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1.
Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy.
Tilma, KK, Bek, T
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2020;(3):236-242
Abstract
BACKGROUND Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. METHODS The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. RESULTS Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. CONCLUSIONS The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy.
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2.
Effects of exercise in combination with autologous bone marrow stem cell transplantation for patients with type 1 diabetes.
Mohamed, MT, Embaby, EA, Labib, A, El-Husseiny, M, Khamis, H, El-Demery, A, Shoukry, MM
Physiotherapy theory and practice. 2019;(12):1233-1242
Abstract
Stem cell therapy is a promising approach for the treatment of type 1 diabetes mellitus (T1D). Previous studies recommended regular exercise for the control of T1D. Experimental studies showed that a combination of stem cells and exercise yielded a better outcome. Yet, the effect of exercise programs following stem cell transplantation in patients with T1D has not been investigated. Thus, the current study aimed to examine the effect of a combined exercise program on measures of glycemic control in patients with T1D who received autologous bone marrow stem cell transplantation (ABMSCT). Thirty patients with controlled T1D were assigned into two equal groups. Both groups underwent ABMSCT and received insulin therapy and a diabetic diet regime. Only the exercise group followed the combined exercise program. Outcome measures of glycemic control (i.e. fasting blood glucose level [FBG], post-prandial blood glucose level [PPG], HbA1c, daily insulin dosage, and C-peptide levels) were tested before and after a 3-month rehabilitation period. There were significant (p < 0.05) decreases in all outcome measures except C-peptides after ABMSCT compared with before in both groups. Moreover, there was a significant decrease in the mean value of HbA1c in the exercise group compared with the control group after rehabilitation. Overall, this study strengthens the idea that adding exercise to ABMSCT is important to help control diabetes in patients with T1D.
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3.
Type 1 diabetes modulates cyclooxygenase- and nitric oxide-dependent mechanisms governing sweating but not cutaneous vasodilation during exercise in the heat.
Fujii, N, Dervis, S, Sigal, RJ, Kenny, GP
American journal of physiology. Regulatory, integrative and comparative physiology. 2016;(6):R1076-R1084
Abstract
Both cyclooxygenase (COX) and nitric oxide synthase (NOS) contribute to sweating, whereas NOS alone contributes to cutaneous vasodilation during exercise in the heat. Here, we evaluated if Type 1 diabetes mellitus (T1DM) modulates these responses. Adults with (n = 11, 25 ± 5 yr) and without (n = 12, 24 ± 4 yr) T1DM performed two bouts of 30-min cycling at a fixed rate of heat production of 400 W in the heat (35°C); each followed by a 20- and 40-min recovery period, respectively. Sweat rate and cutaneous vascular conductance (CVC) were measured at four intradermal microdialysis sites treated with either 1) lactated Ringer (vehicle control site), 2) 10 mM ketorolac (nonselective COX inhibitor), 3) 10 mM NG-nitro-l-arginine methyl ester (nonselective NOS inhibitor), or 4) a combination of both inhibitors. In nondiabetic adults, separate and combined inhibition of COX and NOS reduced exercise sweat rate (P ≤ 0.05), and the magnitude of reductions were similar across sites. In individuals with T1DM, inhibition of COX resulted in an increase in sweat rate of 0.10 ± 0.09 and 0.09 ± 0.08 mg ·: min-1 ·: cm-2 for the first and second exercise bouts, respectively, relative to vehicle control site (P ≤ 0.05), whereas NOS inhibition had no effect on sweating. In both groups, NOS inhibition reduced CVC during exercise (P ≤ 0.05), although the magnitude of reduction did not differ between the nondiabetic and T1DM groups (exercise 1: -28 ± 10 vs. -23 ± 8% max, P = 0.51; exercise 2: -31 ± 12 vs. -24 ± 10% max, P = 0.38). We show that in individuals with T1DM performing moderate intensity exercise in the heat, NOS-dependent sweating but not cutaneous vasodilation is attenuated, whereas COX inhibition increases sweating.
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4.
Glucose concentrations in blood and tissue - a pilot study on variable time lag.
Chlup, R, Krejci, J, O'Connell, M, Sebestova, B, Plicka, R, Jezova, L, Brozova, T, Doubravova, B, Zalesakova, H, Durajkova, E, et al
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2015;(4):527-34
Abstract
AIM: The aim of this pilot study was to acquire insight into the parameters of glycaemic control, especially, (1) the time delay (lag phase) between plasma and tissue glucose concentrations in relation to rise and fall in glucose levels and (2) the rate of glucose increase and decrease. METHODS Four healthy people (HP), 4 people with type 1diabetes (DM1) and 4 with type 2 diabetes (DM2) underwent concurrent glucose measurements by means of (1) the continuous glucose monitoring system (CGMS-Medtronic), Medtronic-Minimed, CA, USA, calibrated by the glucometer Calla, Wellion, Austria, and, (2) the Beckman II analyser to measure glucose concentrations in venous plasma. Samples were taken on 4 consecutive days in the fasting state and 4 times after consumption of 50 g glucose. Carelink Personal, MS Excel, Maple and Mat lab were applied to plot the evolution of glucose concentration and analyse the results. The time difference between increase and decrease was calculated for HP, DM 1 and DM 2. RESULTS In DM1and DM2, glucose tolerance testing (GTT) resulted in slower transport of glucose into subcutaneous tissue than in HP where the lag phase lasted up to 12 min. The maximum increase/decrease rates in DM1 and DM2 vs HP were 0.25 vs < 0.1 mmol/L/min. CONCLUSION CGMS is shown to provide reliable plasma glucose concentrations provided the system is calibrated during a steady state. The analysis of glucose change rates improves understanding of metabolic processes better than standard GTT.
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5.
Expression of mitochondrial superoxide dismutase in polymorphonuclear leukocytes from patients with type 1 diabetes with and without microvascular complications.
Wegner, M, Rawłuszko-Wieczorek, AA, Araszkiewicz, A, Pioruńska-Stolzmann, M, Zozulińska-Ziółkiewicz, D, Wierusz-Wysocka, B, Jagodziński, PP
Polskie Archiwum Medycyny Wewnetrznej. 2014;(5):239-46
Abstract
INTRODUCTION One of the causes of impaired antioxidant response in patients with type 1 diabetes might be decreased expression of mitochondrial manganese superoxide dismutase (MnSOD). OBJECTIVES The aim of this study was to evaluate the expression of MnSOD on transcript and protein levels in polymorphonuclear leukocytes (PMNLs) from patients with type 1 diabetes and analyze its association with microvascular complications. PATIENTS AND METHODS The MnSOD expression was assessed in PMNLs from 46 patients with type 1 diabetes and 12 age- and sex -matched healthy subjects. The study group was divided into 2 subgroups: with and without microvascular complications. The MnSOD expression on the transcript level was evaluated by real -time quantitative polymerase chain reaction, while that on the protein level by Western blot analysis. RESULTS A significant increase in the MnSOD transcript level was observed in all patients with diabetes with and without microvascular complications (P = 0.01, P = 0.02, respectively). The MnSOD protein level was higher in patients without microvascular complications compared with those with complications and the control group (P = 0.05, P = 0.03, respectively). The MnSOD expression was positively correlated with fasting plasma glucose and total cholesterol levels both at the transcript level (r = 0.4, P <0.05 for both correlations) and at the protein level (r = 0.3 and r = 0.4, respectively, P <0.05). CONCLUSIONS Although an increased MnSOD transcript level in patients with type 1 diabetes suggests enhanced antioxidant mobilization in all diabetic patients, decreased levels of the MnSOD protein in PMNLs from patients with microvascular complications compared with those without complications indicates that patients with microvascular complications may have impaired antioxidant response.
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6.
Effects of honey, sucrose and glucose on blood glucose and C-peptide in patients with type 1 diabetes mellitus.
Abdulrhman, M, El Hefnawy, M, Ali, R, Abdel Hamid, I, Abou El-Goud, A, Refai, D
Complementary therapies in clinical practice. 2013;(1):15-9
Abstract
UNLABELLED This study was a case control cross sectional study that was conducted on 50 patients with type 1 diabetes mellitus and 30 controls without diabetes. The mean age of patients was 10.02 years. Oral sugar tolerance tests using glucose, sucrose and honey and measurement of fasting and postprandial serum C-peptide levels were done for all subjects in three separate sittings. The glycemic index (GI) and the peak incremental index (PII) were then calculated for each subject. Honey, compared to sucrose, had lower GI and PII in both patients and controls (P < 0.01). In both patients and controls, the increase in the level of C-peptide after honey was significant when compared with either glucose or sucrose (P < 0.01). CONCLUSION Because of its possible stimulatory effect on diseased beta cells, honey might be considered in future therapeutic trials targeting beta cells of pancreas.
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7.
Neurovascular dysfunction precedes neural dysfunction in the retina of patients with type 1 diabetes.
Lasta, M, Pemp, B, Schmidl, D, Boltz, A, Kaya, S, Palkovits, S, Werkmeister, R, Howorka, K, Popa-Cherecheanu, A, Garhöfer, G, et al
Investigative ophthalmology & visual science. 2013;(1):842-7
Abstract
PURPOSE A variety of studies have shown that flicker-induced vasodilatation is reduced in patients with diabetes. It is, however, unclear whether reduced neural activity or abnormal neurovascular coupling is the reason for this phenomenon. In the present study, we hypothesized that retinal neurovascular dysfunction precedes neural dysfunction in patients with early type 1 diabetes. METHODS In the present study, 50 patients with type 1 diabetes without retinopathy and 50 healthy age- and sex-matched control subjects were included. The retinal vascular response to flicker stimulation was measured using the dynamic Retinal Vessel Analyzer. In addition, the response in retinal blood velocity to flicker stimulation as assessed with laser Doppler velocimetry was studied in a subgroup of patients. Pattern electroretinography (ERG) was used to measure neural retinal function. RESULTS The flicker responses of both retinal arteries and veins were significantly reduced in patients with diabetes (veins in the diabetic group: 3.5 ± 2.3% versus healthy control group: 4.6 ± 2.0%; P = 0.022 between groups, whereas arteries in the diabetic group: 2.0 ± 2.7% versus healthy control group: 3.8 ± 1.7%; P < 0.001 between groups). Likewise, the response of retinal blood velocity was reduced in patients with diabetes, although adequate readings could only be obtained in a subgroup of subjects (diabetic group [n = 22]: 19 ± 7%; healthy control group [n = 24]: 43 ± 19% P < 0.001 between groups). The parameters of pattern ERG were not different between the two groups. CONCLUSIONS The study confirms that flicker responses are reduced early in patients with type 1 diabetes. This is seen before alterations in pattern ERG indicating abnormal neurovascular coupling.
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8.
Sitagliptin as add-on therapy in insulin deficiency: biomarkers of therapeutic efficacy respond differently in type 1 and type 2 diabetes.
Giampietro, O, Giampietro, C, Bartola, LD, Masoni, MC, Matteucci, E
Drug design, development and therapy. 2013;:99-104
Abstract
BACKGROUND Sitagliptin has been proven to be effective and safe as add-on to insulin in adult patients with type 2 diabetes and absolute insulin deficiency. Recently, it has been suggested to extend the use of dipeptidyl-peptidase-4 inhibitors to type 1 diabetes. The aim of this study was to evaluate and compare the effects of a long-term, fixed-dose combination of sitagliptin and metformin as add-on to insulin on body mass index, fasting plasma glucose, fructosamine, HbA(1c), lipids, and daily dose of insulin in both type 1 diabetes and insulin-treated type 2 diabetes. METHODS We recruited 25 patients with type 1 diabetes (mean age 51 ± 10 years, mean disease duration 26 ± 13 years) and 31 insulin-treated type 2 diabetic patients (mean age 66 ± 8 years, mean disease duration 19 ± 9 years), who received sitagliptin with metformin as a fixed-dose combination (50/1000 mg once or twice daily) or sitagliptin (100 mg once daily, if intolerant to metformin) in addition to ongoing insulin therapy for 46 ± 19 weeks and 56 ± 14 weeks, respectively. RESULTS After 21 ± 9 weeks, patients with type 1 diabetes had a significantly lower body mass index, fasting plasma glucose, fructosamine, HbA(1c), and daily insulin requirement. After 49 ± 17 weeks, they maintained their weight loss and total daily insulin dose and showed a significant reduction in low-density lipoprotein cholesterol levels, whereas their HbA(1c) had returned to baseline values. In patients with type 2 diabetes, long-term treatment remained weight-neutral but had persistent beneficial effects on short-term, intermediate-term, and long-term biomarkers of metabolic control, as well as on low-density lipoprotein cholesterol levels and insulin requirement. CONCLUSION Clinical outcomes differed according to type of diabetes in terms of quality and over time. In type 2 diabetes, the combination therapy significantly improved metabolic control and the lipid profile, and decreased insulin requirements, even in the absence of clinically significant weight loss. In type 1 diabetes, the combined therapy only temporarily improved metabolic control, but significantly decreased body weight, low-density lipoprotein cholesterol levels, and insulin requirements.
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9.
Prevention of hypoglycemia by using low glucose suspend function in sensor-augmented pump therapy.
Danne, T, Kordonouri, O, Holder, M, Haberland, H, Golembowski, S, Remus, K, Bläsig, S, Wadien, T, Zierow, S, Hartmann, R, et al
Diabetes technology & therapeutics. 2011;(11):1129-34
Abstract
BACKGROUND Severe hypoglycemic episodes are a barrier for achieving optimal glycemic control. Sensor-augmented pump (SAP) therapy with insulin in combination with a novel mechanism of automatic insulin shutoff (low glucose suspend [LGS]) can be used to prevent and reduce hypoglycemia. In a prospective study, we investigated the effect of the LGS algorithm on the frequency of hypoglycemia in children and adolescents with type 1 diabetes under real-life conditions. METHODS Twenty-one patients with type 1 diabetes (10.8±3.8 years old, duration of diabetes 5.9±3.0 years, pump therapy for 3.7±1.7 years, glycated hemoglobin level 7.8±1.1%) from three pediatric centers used the Paradigm(®) Veo(™) system (Medtronic Minimed, Northridge, CA) during two subseqent time periods: SAP without LGS for 2 weeks and then SAP with LGS enabled for 6 weeks. The primary objective was to assess the frequency of hypoglycemic episodes when using the LGS feature with an insulin delivery shutoff of a maximum of 2 h at a sensor glucose level below 70 mg/dL (3.9 mmol/L). RESULTS In total, 1,298 LGS alerts occurred (853 shorter than 5 min). Forty-two percent of LGS activations (>5 min) lasted less than 30 min, whereas 24% had a duration of 2 h. The number of hypoglycemic excursions (average/day) was reduced during SAP+LGS (<70 mg/L, 1.27±0.75 vs. 0.95±0.49, P=0.010; ≤40 mg/dL, 0.28±0.18 vs. 0.13±0.14, P=0.005) as was the time spent in hypoglycemia (average minutes/day, 101±68 vs. 58±33, P=0.002) without significant difference in the mean glucose level (145±23 vs. 148±19 mg/dL). No episodes of severe hyperglycemia or diabetic ketoacidosis were observed following LGS activation. CONCLUSIONS The present investigation provides evidence that SAP with LGS reduces the frequency of hypoglycemia without compromising safety.
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10.
Effects of a mixed meal on hemodynamics and autonomic control of the heart in patients with type 1 diabetes.
Cozzolino, D, Furlan, R, Gruosso, D, Di Maggio, C, Miraglia Del Giudice, E, Torella, R, Giugliano, D
The Journal of clinical endocrinology and metabolism. 2010;(1):194-200
Abstract
CONTEXT Food intake induces relevant cardiovascular changes together with parallel increases in cardiac sympathetic activity and insulin plasma levels in man. OBJECTIVE We evaluated hemodynamics, neurohormones, and cardiac autonomic control after eating in patients with type 1 diabetes, a disease characterized by the absence of basal and stimulated insulin production. DESIGN AND SETTING Fifteen type 1 diabetic patients and 15 healthy controls underwent blood sampling, electrocardiogram, blood pressure and respiration recordings, and heart rate variability analysis while recumbent, during the 70 degrees head-up tilt, and 20 min after a mixed meal; on another occasion, diabetic patients were also studied 20 min after a mixed meal preceded by their scheduled bolus of exogenous insulin. Spectrum analysis of RR interval provided the indices of sympathetic (LF(RR)) and vagal (HF(RR)) modulation of the sinoatrial node. RESULTS At baseline, no significant differences were found between groups, except for metabolic parameters. Compared with baseline, heart rate, plasma catecholamines, and LF(RR) significantly (P < 0.005) increased, whereas HF(RR) significantly (P < 0.0001) decreased during the tilt in all subjects. Compared with baseline, plasma norepinephrine, heart rate, and LF(RR) significantly (P < 0.05) increased, whereas HF(RR) significantly (P < 0.02) decreased after eating in controls but not in diabetic patients (with and without insulin administered before eating). In both controls and diabetic patients, no relationship between postprandial changes of insulin and LF(RR) and HF(RR) was found. CONCLUSIONS Hemodynamic, neurohormonal, and cardiac neural responses to eating are abnormal in type 1 diabetic patients, independently of insulin.