scholarly journals Renal activity of Akt kinase in experimental Type 1 diabetes

2008 ◽  
pp. 709-716
Author(s):  
J Ždychová ◽  
J Veselá ◽  
L Kazdová ◽  
R Komers

Akt kinase regulates numerous cell functions including glucose metabolism, cell growth, survival, protein synthesis, and control of local hemodynamics. mTOR is one of down-stream effectors of Akt involved in the initiation of protein translation. However, renal Akt signaling in Type 1 diabetes (DM) in vivo, in particular under the conditions reflecting differences in metabolic control, has received less attention. Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels of glycemic control (blood glucose 22.0±1.0, 13.4±1.5, 8.1±0.4 mmol/l, p<0.05 between the groups), achieved by varying insulin treatment (0, 4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration. Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs. C), partially restored in moderately hyperglycemic rats (D-4, -30 %, p<0.05 vs. C), and normalized in D rats with intensive insulin and tight metabolic control (D-12). Expression of active mTOR paralleled Akt activity in D-0 (-51 %, p<0.01 vs. C), but not in D-4 and D12 that demonstrated increases in active mTOR (+55 %, +80 % resp., p<0.05) as compared to C. Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4. In conclusion, glycemic control and intensity of insulin treatment are important modulators of renal Akt and mTOR activity in diabetes. While Akt activity is reversible by tight metabolic control, combination of hyperglycemia and insulin treatment resulted in enhancement of mTOR activity. In addition to Akt, other signaling pathways likely contribute to regulation of renal mTOR activity in diabetes.

2012 ◽  
Vol 69 (7) ◽  
pp. 569-575 ◽  
Author(s):  
Jelena Stojanovic ◽  
Dragoslav Milosevic ◽  
Ilija Antovic ◽  
Goran Sekulic ◽  
Teodora Beljic-Zivkovic

Background/Aim. Despite of contemporary diabetes mellitus (DM) treatment, one half of patients do not achieve an optimal metabolic control. Considering great psychological burden of diabetic patients, the purpose of this study was to assess the effect of different insulin treatment regimens, glycemic control and the presence of vascular complications on self-reported well-being and quality of life (QoL) of subjects with type 1 DM. Methods. The patients with type 1 DM (n = 122) recruited from the outpatient Diabetes Endocrinology Clinic of Zvezdara University Medical Center were divided into 4 groups according to the specific treatment regimen: 26 were on continuous subcutaneous insulin infusion (CSII), 30 on conventional insulin therapy, 33 on multiple daily injections (MDI) with human insulins, and 33 on MDI with insulin analogues. QoL was assessed by self-reported well-being with the following questionnaires: WHO-5 item Well Being Index (WHO- 5), 36 item Short Form (SF-36) survey, and Insulin Treatment Appraisal Scale (ITAS). Objective metabolic control was assessed by glycosylated hemoglobin (HbA1c), lipid levels and the presence of vascular complications. Statistical analyses used in this crosssectional study included: descriptive statistics, Student?s t-test, Chisqare test, contingency tables, ANOVA and correlation methods. Results. The patients on CSII had significantly better metabolic control than all other treatment groups, especially when compared to the one on conventional therapy (CSII HbA1c 7.07 ? 1.48% vs conventional therapy, HbA1c 10.04 ? 1.44; p = 0.000). No significant difference in glycemic control was observed between patients on MDI with human insulins and insulin analogues. Good glycemic control significantly influenced the reported QoL. The patients with retinopathy and nephropathy reported significantly lower physical well-being, and the patients with polyneuropathy and cardiovascular complications reported also lower psychological well being. Conclusions. Insulin treatment regiment selection affects not only objective metabolic control, but also QoL.


2022 ◽  
Vol 11 (2) ◽  
pp. 286
Author(s):  
Isabel Leiva-Gea ◽  
Maria F. Martos-Lirio ◽  
Ana Gómez-Perea ◽  
Ana-Belen Ariza-Jiménez ◽  
Leopoldo Tapia-Ceballos ◽  
...  

Aims: To evaluate the relationship between daily sensor scan rates and changes in HbA1c and hypoglycemia in children. Methods: We enrolled 145 paediatric T1D patients into a prospective, interventional study of the impact of the FreeStyle Libre 1 system on measures of glycemic control. Results: HbA1c was higher at lower scan rates, and decreased as the scan rate increased to 15–20 scans, after which it rose at higher scan rates. An analysis of the change in hypoglycemia, based on the number of daily sensor scans, showed there was a significant correlation between daily scan rates and hypoglycemia. Subjects with higher daily scan rates reduced all levels of hypoglycaemia. Conclusions: HbA1c is higher at lower scan rates, and decreases as scan rate increases. Reductions in hypoglycemia were evident in subjects with higher daily scan rates.


2004 ◽  
Vol 7 (2) ◽  
pp. 14-19
Author(s):  
CAMILLO RICORDI

The discovery of insulin changed the course of history in the treatment of diabetes. However, despite tremendous progress in insulin formulations and treatment strategies, insulin treatment still cannot fully prevent chronic complications and intensive insulin treatment to improve metabolic control, has often paralleled an increased risk of severe hypoglycemia. A cure for Type 1 diabetes should include: ? Restoration of self tolerance, to prevent recurrence of autoimmunity ? Restoration of physiologic metabolism by replacement of the biologic function (insulin producing cells) that was partially of completely impaired as a result of the disease process. ? Prevention of destruction of the new insulin producing cells by the recipient immune system in the absence of any treatment that could introduce an additional risk to the patient, which could be comparable to, or higher than the risk imposed by disease progression under exogenous insulin treatment. Pancreatic islets could be considered an ideal and more physiologic alternative to insulin, as they can restore metabolic control after transplantation, preventing the development of chronic complications. In fact, islets are capable of perfectly timed insulin release and can keep glucose levels in the normal range, functioning for an entire lifetime, if they are not destroyed by the recipient's immune system. Significant progress has been recently reported in the translational research approach towards the development of a cure for Type 1 diabetes. There is now strong evidence for the technical feasibility of human islet isolation and purification procedures. Proof of function of isolated human islets has been clearly established both in animal models and in pilot clinical trials of human islet allotransplantation in patients with surgical and Type 1 diabetes. Additional research in now needed to improve the current clinical results in terms of long term prevention of rejection and recurrence of autoimmunity, the development of safe, non diabetogenic immunomodulation strategies and ultimately the achievement of donor specific immune tolerance. If success will be achieved in these areas, then we will face the critical challenge of identifying sufficient and suitable sources of insulin producing tissue to treat the increasing number of patients who could benefit from this form of therapy and which would not be limited to Type 1 diabetes. That is why the work on xenogeneic islets, embryonic and adult stem cells, islet regeneration and proliferation, as well as engineering of insulin producing cells must be continued, to identify the most ideal source of insulin producing tissue that could be utilized on a large scale once the impediments and limitations of immunosuppression will be resolved.


2009 ◽  
Vol 40 (1) ◽  
pp. 95-103 ◽  
Author(s):  
S. Ohmann ◽  
C. Popow ◽  
B. Rami ◽  
M. König ◽  
S. Blaas ◽  
...  

BackgroundThe relationship between metabolic control and cognitive function in adolescents with type 1 diabetes (DM type 1) is not clear. We compared the quality of glycemic control (GC) and cognitive measures in adolescents with DM type 1 to find out if the quality of diabetes management is related to cognitive impairment.MethodWe assessed executive functions (EFs) and other neuropsychological and psychosocial variables in 70 adolescent patients with DM type 1 and 20 age-matched controls. Patients were divided into two groups according to their last hemoglobin A1c (HbA1c): acceptable (HbA1c 5.9–8.0%, mean 6.9%, 36 patients, mean age 14 years) and non-optimal (HbA1c 8.2–11.6%, mean 9.3%, 34 patients, mean age 15.6 years).ResultsWe found impaired EFs, mainly problems of concept formation (p=0.038), cognitive flexibility (p=0.011) and anticipation (p=0.000), in the patients with DM type 1. Both groups did not differ in intelligence, most assessed EFs and adjustment to chronic illness (Youth Self-Report; YSR). Younger patients (<15 years) were cognitively less flexible. GC was worse in older patients and in patients with longer duration of the disease. We also found significant differences between patients with diabetes and controls concerning somatic complaints, internalizing problems (Child Behavior Checklist; CBCL) and social activity (CBCL and YSR).ConclusionsDM type 1 is associated with cognitive deficits in adolescents independent of the quality of metabolic control and the duration of the disease. These deficits are probably related to the disease, especially in patients with early-onset diabetes.


2021 ◽  
Vol 9 (2) ◽  
pp. e002494
Author(s):  
Claudia Boettcher ◽  
Sascha R Tittel ◽  
Thomas Meissner ◽  
Bettina Gohlke ◽  
Rainer Stachow ◽  
...  

IntroductionTo evaluate sex differences in people with type 1 diabetes concerning changes in glycemic control and trends in insulin pump use and insulin dose over two decades in adolescents and one-and-a-half decades in adults.Research design and methodsPeople aged 10–20 years (data years 1999–2018) and 21–40 years (data years 2004–2018) with type 1 diabetes were identified in the Diabetes Prospective Follow-up Registry (DPV). All available patients’ data sets of the respective period were used for linear regression analyses to investigate trends in HbA1c, pump use, insulin doses and body mass index SD scores (BMI-SDS) in females and males. In addition, stratification by migrant background was made for the adolescent group.ResultsIn the youth group (n=68 662), both boys and girls showed an HbA1c decrease over the period examined. After stratification for migrant background, an HbA1c convergence between boys and girls was seen in those without migrant background as of 2016. Usage of insulin pumps increased continuously from 3% (boys and girls) to 47% (boys) and 54% (girls), respectively. The daily insulin dose in units per kilogram body weight and day increased continuously from 1999 to 2018. An insulin dose leveling between boys and girls occurred. BMI-SDS consistently increased in girls whereas only slight variations were observed in boys.The adult group (n=15 380) showed constant HbA1c sex differences from 2004 to 2018 with lower HbA1c level in females. The use of insulin pump therapy rose from 18% to 35% (males) and 30% to 50% (females).ConclusionsThe gap in metabolic control between boys and girls with type 1 diabetes seems to close, but predominantly in adolescents without a migrant background. Improved HbA1c was associated with increased insulin pump use, especially in girls.In adult patients, sex differences in metabolic control and insulin pump use persist: women show constantly lower HbA1c values and higher insulin pump use.


2018 ◽  
Vol 6 (8) ◽  
pp. 1431-1434 ◽  
Author(s):  
Feyzi Gokosmanoglu ◽  
Attila Onmez

Objective: The purpose of providing and maintaining a proper metabolic control is to prevent the development of chronic complications. In this study, we aimed to determine the influence of flexible insulin dosing with carbohydrate counting method on metabolic and clinical parameters in type 1 diabetes patients.Material and Method: This study was conducted with patients following up at the Endocrinology Clinic with a diagnosis of type 1 diabetes mellitus between 2012 and 2015. Metabolic and clinical parameters before and after carbohydrate counting were compared.Results: Forty patients were included to the study. Of the patients, 40% (n=16) were female and 60% (n=24) were male, and mean age was 21.5±7 year at the time of diagnosis. Statistically significant differences were not detected when hemoglobin A1c, fasting plasma glucose, post-prandial glucose, LDL-cholesterol, and HDL-cholesterol levels were compared at standard dose insulin use and after carbohydrate counting (p<0.005). Among the parameters measured when the patients received standard dose insulin without counting carbohydrate and flexible insulin dosing by counting carbohydrate, statistically significant differences were not detected for baseline insulin dose, bolus insulin dose, triglyceride level, body mass index, or monthly hypoglycemia episodes (p>0.05).Conclusion: Flexible insulin dosing with carbohydrate counting provides significant improvements in clinical and metabolic control. We detected improvements in lipid profiles and glycemic control. Additionally, patients generally did not gain weight despite flexible nutrition, and frequency of hypoglycemia remained unchanged despite strict glycemic control.OBJECTIVE: The purpose of providing and maintaining a proper metabolic control is to prevent the development of chronic complications. In this study, we aimed to determine the influence of flexible insulin dosing with carbohydrate counting method on metabolic and clinical parameters in type 1 diabetes patients.MATERIAL AND METHODS: This study was conducted with patients following up at the Endocrinology Clinic with a diagnosis of type 1 diabetes mellitus between 2012 and 2015. Metabolic and clinical parameters before and after carbohydrate counting were compared.RESULTS: Forty patients were included in the study. Of the patients, 40% (n = 16) were female, and 60% (n = 24) were male, and mean age was 21.5 ± 7 year at the time of diagnosis. Statistically significant differences were not detected when haemoglobin A1c, fasting plasma glucose, post-prandial glucose, LDL-cholesterol, and HDL-cholesterol levels were compared at standard dose insulin use and after carbohydrate counting (P < 0.005). Among the parameters measured when the patients received standard dose of insulin without counting carbohydrate and flexible insulin dosing by counting carbohydrate, statistically, significant differences were not detected for baseline insulin dose, bolus insulin dose, triglyceride level, body mass index, or monthly hypoglycemia episodes (P > 0.05).CONCLUSION: Flexible insulin dosing with carbohydrate counting provides significant improvements in clinical and metabolic control. We detected improvements in lipid profiles and glycemic control. Additionally, patients generally did not gain weight despite flexible nutrition, and frequency of hypoglycemia remained unchanged despite strict glycemic control.


2004 ◽  
Vol 4 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Indira Kulenović ◽  
Senija Rasić ◽  
Mirko Grujić

ABSTRACTINTRODUCTION: Without sufficient insulin treatment, acceptable level of glycoregulation, avoidance of dislipoproteinaemia and maintaince of body mass is difficult to achieve in patients with type 1 diabetes mellitus (DM). On the other hand sometimes it is difficult to prevent weight gain, endogenous hyperlipidemia and iatrogenic insulin resistance.AIM: To compare metabolic control indicators in patients with type 1 DM in patients treated conventionally to those on intensified insulin regimen.MATERIAL AND METHODS: A sample of 52 persons with type 1 DM, without late complications and long duration of the disease, was selected. Among them 19 (36.5%) persons were treated with insulin in 4 or 5 doses, and 33 (63.5%) conventionally, in 2 doses. All the participants had biochemical indicators of metabolic control determined (glycosylated Hb, fasting and postprandial glycaemia, total cholesterol, triglycerides as well as lipoprotein fractions, HDLC and LDLC), body height (BH) and weight (BW) measured, body mass index calculated (BMI) and blood pressure measured (BP).RESULTS: In the group treated conventionally we found significantly higher mean values of BMI as compared to those on intensified insulin treatment (23.2 ± 2.0 kg/m2, and 21.2 ± 1.2 kg/m2 respectively, p<0.01) and proportion of those with overweight was as well significantly higher (27.3% versus 0%, p =0.012). We noted higher mean values of systolic (134.2 ± 17.6 mmHg, versus 123.4 ± 12.7. p<0.05) and diastolic (83.2 ± 10.1, versus 74.0 ± 9.7, p<0.01) BP. Biohemical indicators of gly-coregulation were significantly worse with, at the same time, higher total dose of applied insulin (55.9 ± 8.5 IU, versus 46.3 ± 10.0 IU, p <0.01), and insulin units per kg of body weight (0.84 ± 0.11 IU/kg versus 0.77 ± 0.15 IU/kg, p<0.05).CONCLUSION: Results indicate that intensified insulin treatment is more favourable variant of treatment, by which the certain level of insulin resistance, which might be present in patients treated with two higher insulin doses, is probably reduced. Therefore it improves metabolic outputs, blood pressure values and body mass index but also may have beneficial impact to economic aspect of insulin treatment as well.


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