Plasma endothelin-1 and total insulin exposure in diabetes mellitus

1999 ◽  
Vol 97 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Flemming WOLLESEN ◽  
Lars BERGLUND ◽  
Christian BERNE

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relationship, and ET-1 effects on vascular wall structure are similar to the long-term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their total insulin exposure to see if plasma ET-1 might be a link between insulin exposure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight glycaemic control for 2 years in a cross-sectional design. We measured basal and glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinfold thickness, glomerular filtration rate, albumin excretion rate and standard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Type II diabetes. Patients with an albumin excretion rate > 300 μg/min were excluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 normal subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in Type II diabetes (P = 0.0001). In all patients with measurable plasma C-peptide, plasma ET-1 was associated with basal plasma C-peptide (r = 0.5018, P < 0.0001), with stimulated plasma C-peptide (r = 0.5379, P < 0.0001), and with total daily insulin dose (r = 0.2219, P = 0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily insulin dose. Our study shows that the plasma concentration of ET-1 is closely associated with insulin secretion and insulin dose in patients with diabetes. Plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Increased insulin exposure in patients with diabetes may have long-term effects on vascular wall structure through its stimulation of ET-1 expression.

Author(s):  
O. L. Moskalenko ◽  
O. V. Smirnova ◽  
E. V. Kasparov ◽  
I. E. Kasparova

The article is devoted to the study of psychoemotional characteristics of patients with diabetes mellitus. Conducting psychological techniques, testing, questioning patients will reveal anxiety-depressive states and psychological characteristics of patients with type I diabetes and type II diabetes for successful disease control. It is necessary to strive for the examination of such patients with an individual approach for each. To improve the quality of life of such patients, it is necessary to search for effective approaches in the education system of patients with type I diabetes and type II diabetes with the participation of psychologists.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Lawrence S. Gazda ◽  
Horatiu V. Vinerean ◽  
Melissa A. Laramore ◽  
Richard D. Hall ◽  
Joseph W. Carraway ◽  
...  

We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin (n=3) was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652) when compared to a first macrobead implantation (days 9, 21, and 21) in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years) implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1380 ◽  
Author(s):  
Swayam Prakash Srivastava ◽  
Julie E. Goodwin

The available evidence suggests a complex relationship between diabetes and cancer. Epidemiological data suggest a positive correlation, however, in certain types of cancer, a more complex picture emerges, such as in some site-specific cancers being specific to type I diabetes but not to type II diabetes. Reports share common and differential mechanisms which affect the relationship between diabetes and cancer. We discuss the use of antidiabetic drugs in a wide range of cancer therapy and cancer therapeutics in the development of hyperglycemia, especially antineoplastic drugs which often induce hyperglycemia by targeting insulin/IGF-1 signaling. Similarly, dipeptidyl peptidase 4 (DPP-4), a well-known target in type II diabetes mellitus, has differential effects on cancer types. Past studies suggest a protective role of DPP-4 inhibitors, but recent studies show that DPP-4 inhibition induces cancer metastasis. Moreover, molecular pathological mechanisms of cancer in diabetes are currently largely unclear. The cancer-causing mechanisms in diabetes have been shown to be complex, including excessive ROS-formation, destruction of essential biomolecules, chronic inflammation, and impaired healing phenomena, collectively leading to carcinogenesis in diabetic conditions. Diabetes-associated epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndMT) contribute to cancer-associated fibroblast (CAF) formation in tumors, allowing the epithelium and endothelium to enable tumor cell extravasation. In this review, we discuss the risk of cancer associated with anti-diabetic therapies, including DPP-4 inhibitors and SGLT2 inhibitors, and the role of catechol-o-methyltransferase (COMT), AMPK, and cell-specific glucocorticoid receptors in cancer biology. We explore possible mechanistic links between diabetes and cancer biology and discuss new therapeutic approaches.


1998 ◽  
Vol 95 (3) ◽  
pp. 331-337 ◽  
Author(s):  
K. KRAPFENBAUER ◽  
R. BIRNBACHER ◽  
H. VIERHAPPER ◽  
K. HERKNER ◽  
D. KAMPEL ◽  
...  

1.The role of oxidative stress in the pathogenesis of the diabetic state is being investigated extensively. Although oxidative stress has been reported in terms of glycoxidation, protein oxidation and DNA oxidation in diabetes mellitus, oxidation parameters have not been determined in parallel on the same study population. 2.We studied 24 patients with diabetes mellitus (14 patients with Type I diabetes with a mean age of 62.3±6.3 years and 10 patients with Type II diabetes aged 67.3±5.9 years) and compared them with age-matched non-diabetic controls. Urinary o-tyrosine, 8-hydroxy-2′-deoxyguanosine and pentosidine measurements by HPLC were made on two occasions (t1 and t2). 3.A clear statistical difference was found between diabetic patients and controls at t1 or t2 for 8-hydroxy-2′-deoxyguanosine and pentosidine, but not for o-tyrosine. No significant correlations were found between clinical and other laboratory parameters except high-density lipoprotein and uric acid. We revealed significantly increased glycoxidation and DNA oxidation in patients with Type I and Type II diabetes, but protein oxidation was not different from controls. 4.The finding of increased glycoxidation reflects increased oxidation of the carbohydrate moiety, whereas the increased levels of oxidized DNA may also be interpreted as due to increased DNA repair. The increased 8-hydroxy-2′-deoxyguanosine does not indicate the generation of an individual active oxygen species, but DNA could have been oxidized simply by alkenals from lipid peroxidation, as e.g. malondialdehyde. As no difference in protein oxidation (i.e. o-tyrosine) between diabetics and controls could be revealed, the oxidation of DNA by hydroxyl radical attack is unlikely, as o-tyrosine was proposed as a marker for hydroxyl radical attack. Therefore, the message is that increased glycoxidation can be confirmed, protein oxidation does not appear to take place and increased DNA oxidation is still not proven, as increased 8-hydroxy-2′-deoxyguanosine may simply reflect repair.


Top Drugs ◽  
2015 ◽  
Author(s):  
Jie Jack Li

Diabetes has been known since antiquity. In fact, the term “diabetes mellitus” comes from the Greek meaning “siphon and honey” due to the excess excretion (siphon or faucet) of hyperglycemic (sweetened, or honeyed) urine associated with diabetes. In ancient times, diabetes was mostly type I, which usually manifests acutely in the young, secondary to certain underlying insults (possibly infections) to the islet cells of the pancreas resulting in an absolute lack of insulin. Insulin was discovered by Banting and Best in 1921, and insulin injection has literally saved millions of lives since then. With the wondrous efficacy that insulin bestows, type I diabetes is largely controlled because type I diabetes is insulindependent. However, type II diabetes, a more prevalent form of diabetes, is not insulin-dependent. In ancient times, when nutrition was scarce and obesity was not prevalent, type II diabetes mellitus (T2DM) was extremely rare. Indeed, type II diabetes is a disease more frequently associated with maturity, obesity, and gradually increasing blood glucose concentrations, and it may be asymptomatic for some time, only discovered on routine glucose screening. In fact, with the increasing body weight of the general population of the developed world, type II diabetes is becoming an epidemic. Serious complications of diabetes include nephropathy (kidney diseases), neuropathy (nerve damage), and retinopathy (blindness). Diabetes is the most common cause of blindness and amputation in the elderly in the United States. Oral diabetes drugs are required for most type II diabetic patients. Diabetes drugs may be classified into four categories: (a) agents that augment the supply of insulin such as sulfonylureas; (b) agents that enhance the effectiveness of insulin such as biguanides and thiazolidinediones; (c) GLP agonists; and (d) DPP4 Inhibitors. The efficacy of all the antidiabetic drugs can be monitored by measuring glycosylated hemoglobin (HaA1c) as a long term marker of elevated blood glucose. The amount of HaA1c reflects the average level over the last 120 days, the life span of a red blood cell, and should remain below 7%.


1997 ◽  
Vol 17 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Emaad M. Abdel-Rahman ◽  
Maureen Wakeen ◽  
Stephen W. Zimmerman

Objectives Long-term experience of patients on peritoneal dialysis (PD) in general, and in diabetic patients specifically, is limited. Few patients have been followed on PD for over 8 years. Our aim was to evaluate and characterize long-term survivors (L TS) on PD for more than 100 months. A retrospective analysis of 20 patients who survived on PD for more than 100 months was performed. Data on long-term survivors was compared to data of 103 patients who died or switched to hemodialysis (HD) in less than 100 months. Design The study included all patients starting PD prior to 1 January 1986. Demographic, biochemical, dialysis prescription, and morbidity data were obtained on these patients. Characteristics of long-term survivors on PD (more than 100 months), was compared with those who died or switched to HD in less than 100 months, using Student t-test. Setting An experienced single center, university-based dialysis program. Patients 165 patients started PD at the University of Wisconsin prior to 1 January 1986. Forty three had type I diabetes mellitus and 24 had type II diabetes mellitus as the cause of their renal failure. Results Twenty patients survived on PD more than 100 months (L TS). Long-term survival of type I diabetic patients was seen in 7 of 43 patients at risk. Seventeen type I diabetics received renal transplants and ten died. 103 patients either died or switched to HD in less than 100 months. Long-term survivors were significantly younger, weighed less, had fewer episodes of peritonitis, fewer hospital days, and were prescribed more dialysis per kg body weight, than those who died or switched to HD prior to 100 months. Conclusions Long-term survival on CAPD for longer than 100 months is possible with survival periods up to 18 years in both males and females and in nondiabetics as well as patients with type I diabetes mellitus. No patient with type II diabetes mellitus survived longer than 100 months on CAPD. In comparison to short-term survivors, long-term survivors were characterized by being younger, weighing less, having fewer episodes of peritonitis, fewer hospital days, and were prescribed more dialysis/kg body weight.


1998 ◽  
Vol 12 (4) ◽  
pp. 208-214 ◽  
Author(s):  
Con Tsalamandris ◽  
Sianna Panagiotopoulos ◽  
Terri J. Allen ◽  
Luke Waldrip ◽  
Bill Van Gaal ◽  
...  

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