scholarly journals Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Metin Guclu ◽  
Ozen Oz Gul ◽  
Soner Cander ◽  
Oguzkaan Unal ◽  
Guven Ozkaya ◽  
...  

Aim.To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM).Material and Methods.A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n=30) or insulin alone (n=31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications.Results.Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64,P=0.006; leptin 25.8 ± 17.6 to 20.1 ± 12.55,P=0.006; group 2: resistin 7.16 ± 2.30 to5.57±2.48,P=0.031; leptin 16.72 ± 16.1 to 14.0 ± 13.4,P=0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98,P=0.015, and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90,P=0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower.Discussion.The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion.

2011 ◽  
Vol 39 (2) ◽  
pp. 377-381 ◽  
Author(s):  
HEINI POHJANKOSKI ◽  
HANNU KAUTIAINEN ◽  
MATTI KORPPI ◽  
ANNELI SAVOLAINEN

Objective.To describe the occurrence and main clinical and laboratory findings of patients having both juvenile idiopathic arthritis (JIA) and diabetes mellitus type 1 (DM-1) in a period of 30 years.Methods.Eighty-two patients having simultaneous JIA and DM-1 were identified in the reimbursement registers of the Finnish National Institute of Insurance during the period 1976–2005. Data on their clinical histories were collected from patient files.Results.Occurrence of simultaneous JIA and DM-1 increased 4.5-fold between the first (1976-85) and the last (1996–2005) decade. Prevalence of uveitis was 7%, of rheumatoid factor seropositivity 15%; 22% of patients had a third autoimmune disease [autoimmune disease (AID)], and 16% had serious psychiatric problems.Conclusion.The occurrence of patients with the 2 diseases, JIA and DM-1, increased over 3 decades. The prevalence of uveitis was low, the number of seropositive patients was high, and further cases of AID were frequent. Patients had multiple additional problems necessitating multiprofessional care.


2014 ◽  
Vol 99 (1) ◽  
pp. 169-177 ◽  
Author(s):  
Dan Nguyen ◽  
W Hsu Jean ◽  
Farook Jahoor ◽  
V Sekhar Rajagopal

Abstract Background HIV-infected patients are reported to have impaired oxidation of fatty acids despite increased availability, suggesting a mitochondrial defect. We investigated whether diminished levels of a key mitochondrial antioxidant, glutathione (GSH), was contributing to defective fatty acid oxidation in older HIV-infected patients, and if so, the metabolic mechanisms contributing to GSH deficiency in these patients. Methods In an open-label design, 8 older GSH-deficient HIV-infected males were studied before and after 14 days of oral supplementation with the GSH precursors cysteine and glycine. A combination of stable-isotope tracers, calorimetry, hyperinsulinemic-euglycemic clamp, and dynamometry were used to measure GSH synthesis, fasted and insulin-stimulated (fed) mitochondrial fuel oxidation, insulin sensitivity, body composition, anthropometry, forearm-muscle strength, and lipid profiles. Results Impaired synthesis contributed to GSH deficiency in the patients and was restored with cysteine plus glycine supplementation. GSH improvement was accompanied by marked improvements in fasted and fed mitochondrial fuel oxidation. Associated benefits included improvements in insulin sensitivity, body composition, anthropometry, muscle strength, and dyslipidemia. Conclusions This work identifies 2 novel findings in older HIV-infected patients: 1) diminished synthesis due to decreased availability of cysteine and glycine contributes to GSH deficiency and can be rapidly corrected by dietary supplementation of these precursors and 2) correction of GSH deficiency is associated with improvement of mitochondrial fat and carbohydrate oxidation in both fasted and fed states and with improvements in insulin sensitivity, body composition, and muscle strength. The role of GSH on ameliorating metabolic complications in older HIV-infected patients warrants further investigation. (J Clin Endocrinol Metab 99: 169–177, 2014)


PLoS Medicine ◽  
2021 ◽  
Vol 18 (7) ◽  
pp. e1003691
Author(s):  
Piero Ruggenenti ◽  
Monica Cortinovis ◽  
Aneliya Parvanova ◽  
Matias Trillini ◽  
Ilian P. Iliev ◽  
...  

Background Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. Methods and findings VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. Conclusions Risk/benefit profile of study treatments was similar. Dual renin–angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. Trial registration EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.


2020 ◽  
Vol 14 (3) ◽  
pp. 63-70
Author(s):  
K. A. Berdyugin ◽  
I. V. Kadyntsev ◽  
O. V. Berdyugina ◽  
E. A. Taskina ◽  
N. G. Kashevarova

Osteoarthritis (OA) is the most common joint disease. Searching for new treatment methods and regimens for OA is relevant.Objective: to evaluate the efficiency and safety of therapy with a symptomatic sustained-release drug (Alflutop) in combination with intra-articular hyaluronic acid (HA) injection versus monotherapy with HA in patients with knee OA in routine clinical practice.Patients and methods. A post-registration open-labeled prospective comparative randomized study was conducted to assess the results of treatment in 76 patients (31 men and 45 women; mean age, 49.3±8.5 years; body mass index, 28.4±0.8 kg/m2 ) in two clinical centers in Yekaterinburg and Perm. The patients were randomized into two equal groups, were homogeneous in terms of gender, the frequency of comorbidities, and vital signs (blood pressure, heart rate, and respiratory rate).Group 1 patients received Alflutop as 1-ml daily intramuscular injections (a total of 20 injections) + 2 ml of 1% intraarticular (IA) HA solution injections three times at 1-week intervals; Group 2 patients were given 2 ml of 1% intraarticular HA solution injections three times at 1-week intervals. As an additional therapy, the use of meloxicam 7.5–15 mg/day was permitted, and, if non-steroidal anti-inflammatory drugs were contraindicated, paracetamol 1–3 g/day might be used.Results and discussion. During treatment, both groups of patients showed improvement (compared to the baseline levels). At the same time, evaluating the intergroup values revealed clear differences: a more pronounced decrease in all WOMAC indicators in Group 1 patients: pain scores, 2 [1; 3] vs. 4 [2; 5] in Group 2 (p<0.001); stiffness, 1 [0; 2] vs. 2 [1; 4] (p<0.001); functional insufficiency, 8 [3; 12] vs. 15.5 [12; 20] (p<0.001); and total WOMAC scores, 12 [7; 13] vs. 21.5 [15; 28] (p<0.001). Pain-intensity assessment using the visual analogue scale also showed the more pronounced positive effect of the combination therapy in Group 1 (p<0.001).Alflutop used in combination with HA was shown to be more preferable than HA monotherapy, which was confirmed by the results achieved for all WOMAC indicators. At 6 months, by the last visit, there were pronounced positive changes in all the analyzed parameters in both groups. At the same time, the most significant changes were recorded in the Alflutop + HA group than in the HA group (p<0.001). Perhaps, the mechanism in exhibiting the found synergistic effect of these drugs lies in their different effect on the pathogenesis of the disease. However, further study of this issue is required in multicenter randomized controlled trials.The good safety of the drugs was confirmed: not a single adverse event was revealed.Conclusion. The patients receiving the combination therapy with Alflutop + HA had the best treatment results in all the parameters assessed.


Cephalalgia ◽  
2003 ◽  
Vol 23 (10) ◽  
pp. 961-962 ◽  
Author(s):  
J Pascual ◽  
R Leira ◽  
JM Láinez

The aim was to explore whether combining a β-blocker and sodium valproate could lead to an advantage in efficacy in patients with migraine previously resistant to the two medications in monotherapy. Fifty-two patients (43 women) with a history of episodic migraine with or without aura, and previously unresponsive to β-blockers and sodium valproate in monotherapy, were treated with a combination of propranolol or nadolol and sodium valproate in an open-label fashion. Eight patients (15%) discontinued due to adverse events. Fifteen (29%) did not respond. The remaining 29 cases (56%) showed response (>50% reduction in migraine days). The response was excellent in nine (17%). From this open trial, combination therapy with a β-blocker and sodium valproate appears to be a good migraine preventative in some previously resistant migraine cases. Controlled trials are now necessary to determine the true advantage in efficacy of this combination in difficult to treat migraineurs.


2019 ◽  
Vol 3 (1) ◽  
pp. 1-6
Author(s):  
Ana Fitria Nusantara ◽  
Sunanto Sunanto ◽  
Achmad Kusyairi

AbstrakKetoasidosis diabetik (KAD) merupakan komplikasi akut diabetes melitus tipe 1 yang ditandai dengan dehidrasi, kehilangan elektrolit, asidosis dan disebabkan oleh pembentukan keton  yang  berlebihan.  Keadaan ini merupakan gangguan metabolisme yang paling serius dan mengancam jiwa. Namun demikian kejadian KAD dapat dicegah dengan beberapa cara, salah satunya adalah dengan menejemen diabetik yang benar. Penelitian bertujuan mengidentifikasidukungan keluarga dalam mencegah ketoasidosis diabetik.Desain penelitian kualitatif digunakan pada penelitian ini dengan pendekatan phenomenology. Data dikumpulkan dengan tehnik wawancara tidak terstruktur kemudian dianalisis dengan tehnik Van Manen.Hasil penelitian menunjukkan  bahwa support sistem keluarga dapat dilakukan dengan cara membawakan bekal makan atau minum untuk kegiatan di luar rumah, mengkomunikasikan penyakit anak kepada pihak lain di luar rumah (sekolah, tetangga, saudara), melakukan injeksi insulin, pengawasan diet, serta kunjungan rutin ke rumah sakit. Anak dengan DM tipe 1 berada pada usia yang sangat muda sehingga dalam hal perawatan dan penatalaksanaan diabetesnya sangat tergantung pada orang tua selaku penanggung jawab dalam perawatan anak. Dukungan orang tua dalam perawatan anak dengan DM tipe 1 sangat berdampak pada pencegahan terjadinya komplikasi seperti ketoasidosis diabetik.Kata kunci: support system, ketoasidosis diabetik, diabetes mellitus tipe 1  AbstractDiabetic ketoacidosis (DKA) is an acute complication of type 1 diabetes mellitus which is characterized by dehydration, loss of electrolytes, acidosis and is caused by excessive ketone formation. This situation is the most serious and life-threatening metabolic disorder. However, the incidence of DKA can be prevented in several ways, one of them is correctly diabetic management. The study aims to identify family support in preventing diabetic ketoacidosis. A qualitative research design was used in this study with a phenomenology approach. Data was collected using unstructured interview techniques and then analyzed with Van Manen techniques. The results showed that family support system are by bringing food or drink supplies to the activities outside the home, communicating children's illnesses to other parties outside the home (school, neighbors, relatives), injecting insulin, supervising diet, and regular visits to hospital. Children with type 1 diabetes are at a very young age so that in case of diabetes care and management aredepent on parents as the responsible person in child care. Parental support to the children with type 1 DM are greatly affects to the prevention of complications such as diabetic ketoacidosis.Keywords: support system, ketoacidosis diabetic, diabetes mellitus type 1


2008 ◽  
Vol 55 (1) ◽  
pp. 43-46
Author(s):  
Z.N. Savic ◽  
P.B. Djordjevic ◽  
M.M. Ilic ◽  
S.S. Popovic ◽  
V. Dimitrijevic-Sreckovic ◽  
...  

Purpose: The aim of this study was measurement of artery intima media thickness (IMT) and plaques as an early indicator of atherosclerosis in diabetics comparing with other risk factors of carotid artery. Methods and Materials: 110 pts: 50 with Diabetes Mellitus, type 1 (25) and type 2 (25), 20 pts with glucose intolerance, 20 pts with type 2 de novo and 20 pts obese without diabetes. Ultrasound examination (using 7.5MHz sound on Toshiba SSA- 270A) end measurement of intima-media ticknes (IMT) were performed on Carotis communis (CCA), bifurcation and distal from bifurcation to a.carotis intern (ACI), expressed in mm. Plaques were correlated with other common factors age, BP, lipid parameters (Chol, HDL, LDL, Triglycerides), smokes, alcoholism and obese (BMI). The authors used 2 test and Spearman?s correlation . Results: The lowest percent of plaques was found in group with type DM 1. The highest percent of plaques was found in type DM 2. Statistically there is highly significant difference between plaques founded on type 2 DM and types 2 DM de novo and on other types. Conclusion: DM is not an independent risk factor for developing of macroangiopathic changes an arterial walls, but their appirience are more presenting in diabetic patients. The highest number of plaques are presenting DM type 2 (29.6%), and after type 2 de novo (26.8%), the next highest position of plaques were in patients with obese but without DM and intolerantio glucosae (IFG+IGT) (17.1%) and type 1 DM (9.8%). Risk factors were presented in following percentage : Obese 80.5% pts; hyperlipidema 53.7% pts; HTA 51.3%; smoking 51.2% pts and alchocholism 2.4% pts. According to these results, all risk factors were included in patophysiology of plack forming except alcoholism. Influences of these risk factors are very importance and their synergic action lids to their rapid appirience and clinical manifestations. DM has specific position in patophisiology of atherosclerosis.


2020 ◽  
Vol 11 (2) ◽  
pp. 71-80
Author(s):  
N. V. Malyuzhinskaya ◽  
K. V. Stepanenko ◽  
E. I. Volchansky

Objective: to assess the functional state of the microvasculature in children with diabetes mellitus type 1 (DM type 1).Materials and methods: 63 children with a verifi ed diagnosis of diabetes mellitus type 1 were examined. Th e control group consisted of 30 practically healthy children. Methods: clinical, paraclinical (determination of glycated hemoglobin level, study of microcirculation indicators using laser Doppler fl owmetry (LDF), statistical.Results: microcirculatory disorders accompanying the course of diabetes mellitus type 1 depending on the length of illness were identifi ed. In children with diabetes mellitus type 1 with standing less than 3 years an increase in the average modulation of blood fl ow mainly due to passive regulation mechanisms and the predominance of hypera adaptation in assessing the functional states of microcirculation of varying severity with an increase in the energy of oscillatory processes were observed. Signs of non-nutritive hyperemia in the zone rich in arteriovenous anastamoses and a decrease in perfusion due to an increase in perfusion fl uctuations and coeffi cient of variation in the distal extremities, as well as a decrease in amplitudes in the active tone-forming range, a gradual decrease in the energy of oscillations and randomness criteria were diagnosed with standing in the duration of the disease.Conclusions: disorders in children with diabetes mellitus type 1 microcirculatory detected using LDF are staged. Th e contribution of non-nutritive blood fl ow to microcirculation increases as the disease progresses, which leads to tissue hypoxia. Evaluation of the combination of energy, information and non-linear parameters of the oscillatory component of the blood flow allows you to identify the type of functional state in the microcirculation system.


2016 ◽  
pp. 118-122
Author(s):  
E. S. Makhlina ◽  
M. P. Kapliyeva ◽  
Ya. L. Navmenova ◽  
I. G. Savasteyeva

Objective: to give complex assessment of compensation in diabetes mellitus type 1 (DM 1) using the continuous glucose monitoring system. Material and methods. The study included 162 patients with DM 1 who were examined using the complex of methods: questionnaire survey, clinical and anamnestic analysis, laboratory investigation of glycohemoglobin level, and continuous glucose monitoring using a CGMS system. Results. The data analysis has showed that only 23% examined patients have adequate control of DM 1. The quality of DM 1 control did not depend on age, DM 1 duration and body mass index (BMI). The highest glycemia variability depended on the total daily dose of injected short action insulin. We have found a high risk for development of hypoglycemia episodes independently of DM 1 quality control. Conclusion. In order to prescribe correct treatment for patients with DM 1, besides the main target criteria of compensation, it is very important to determine the hypoglycemia and hyperglycemia risk indices as well as clinical hypoglycemic reactions for the assessment of DM 1 compensation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jacob Cobb ◽  
Jeffrey Rawson ◽  
Nelson Gonzalez ◽  
Michael Hensel ◽  
Fouad Kandeel ◽  
...  

A therapy that includes an oral vaccine for type 1 diabetes (T1D) using live attenuated Salmonella MvP728 (ΔhtrA/ΔpurD), cytokines (IL10 and TGFβ) and preproinsulin (PPI) antigen in combination with a sub-therapeutic dose of anti-CD3 mAb was developed by our team. The vaccine combination therapy reduced insulitis and prevented and reversed diabetes in non-obese diabetic (NOD) mice. Here, we show the effectiveness of an alternative Salmonella mutant (ΔmsbB) as a carrier strain, which is anticipated to have lower risks of an inflammatory response and septicemia as a result of modification in the lipopolysaccharide (LPS) via detoxification of lipid A. This mutant strain proved to have highly reduced pathogenic side effects. Salmonella strain ΔmsbB expressed autoantigens and in combination with cytokines and anti-CD3 mAb, successfully prevented and reversed T1D to levels comparable to the previously used carrier strain ΔhtrA/ΔpurD. Additionally, the Salmonella msbB mutant resulted in higher rates of host cell infection. These results further demonstrate the potential of an oral Salmonella-based combined therapy in the treatment of early T1D.


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