Mindfulness, disordered eating, and impulsivity in relation to glycemia among adolescents with type 1 diabetes and suboptimal glycemia from the Flexible Lifestyles Empowering Change (FLEX) intervention trial.

OBJECTIVE: To assess the relationship between mindfulness and glycemia among adolescents with type 1 diabetes (T1D) with suboptimal glycemia, and evaluate the potential mediation by ingestive behaviors, including disordered eating, and impulsivity. RESEARCH DESIGN AND METHODS: We used linear mixed models for hemoglobin A1c (HbA1c) and linear regression for continuous glucose monitoring (CGM) to study the relationship of mindfulness [Child and Adolescent Mindfulness Measure (CAMM)] and glycemia in adolescents with T1D from the 18-month Flexible Lifestyles Empowering Change (FLEX) trial. We tested for mediation of the mindfulness-glycemia relationship by ingestive behaviors, including disordered eating (Diabetes Eating Problem Survey-Revised), restrained eating, and emotional eating (Dutch Eating Behavior Questionnaire); and impulsivity (total, attentional, and motor, Barrett Impulsiveness Scale). RESULTS: At baseline, participants (n = 152) had a mean age of 14.9 ± 1.1 years and HbA1c of 9.4 ± 1.2% [79 ± 13 mmol/mol]. The majority of adolescents were non-Hispanic white (83.6%), 50.7% were female, and 73.0% used insulin pumps. From adjusted mixed models, a 5-point increase in mindfulness scores was associated with a -0.19% (95%CI -0.29, -0.08, p = 0.0006) reduction in HbA1c. We did not find statistically significant associations between mindfulness and CGM metrics. Mediation of the relationship between mindfulness and HbA1c by ingestive behaviors and impulsivity was not found to be statistically significant. CONCLUSIONS: Among adolescents with T1D and suboptimal glycemia, increased mindfulness was associated with lower HbA1c levels. Future studies may consider mindfulness-based interventions as a component of treatment for improving glycemia among adolescents with T1D, though more data are needed to assess feasibility and efficacy.

Supplementation of Morin Restores the Altered Bone Histomorphometry in Hyperglycemic Rodents via Regulation of Insulin/IGF-1 Signaling.

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin's protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.

Therapeutic role of Rauwolfia serpentina in minimizing the risk of glycosylation and associated biomarkers in experimentally induced type 1 diabetic mice.

Present work investigates the effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 diabetic mice. Mice were divided into normal, diabetic, negative and positive controls (I-IV) and three test (HyMREt doses) groups (V-VII - 50, 100, &150mg/kg). Allocated treatment of each group was given orally for 14 days in overnight fasted state. Percent change in fasting blood glucose (FBG), body weights, body tissue weights, hepatic glycogen, total lipids, glycosylated hemoglobin (HbA1c), complete blood profile and antioxidant enzymes including catalase (CAT) and superoxide dismutase (SOD) were estimated. HyMREt doses produced meaningful (p<0.0001) reduction (-39 to -53%) in FBG. Hemoglobin (Hb) levels were raised, HbA1c were considerably decreased (4.5-3.77%) and glycosylation (HbA1c to Hb) ratio was expressively (p<0.0001) improved in test groups. Dose-wise improvement (p< 0.05) in total glycogen and decrement (p<0.05) in lipids were observed in livers of test groups. HyMREt significantly decreased (p<0.05) percent inhibition of SOD and CAT. HyMREt doses progressively (p<0.05) improved RBC and other hematological parameters while decrement was only noticed in leucocyte counts. Administration of test doses of HyMREt were significantly reduced the glycosylation, oxidative stress and anemia caused by alloxan intoxication in mice.

Effect of antioxidant treatment with n-acetylcysteine and swimming on lipid expression of sebaceous glands in diabetic mice.

The sebaceous gland (SG) is involved in different inflammatory, infectious and neoplastic processes of the skin and can be related to specific diseases, e.g., diabetes mellitus. Sometimes, the histological diagnosis requires complementary tests due to the ability of diseases to mimic other tumors. We evaluated the sebaceous gland density in Non-obese diabetic mice to analyze the N-acetylcystein effects and swimming exercise treatment in sebaceous glands healing, using specific staining in histochemistry and immunohistochemistry reactions in the identification of the lipid expression in the sebaceous gland. We investigated the intracytoplasmic lipid expression and analysis of gland density from SG in dorsal skin samples from the Non-obese diabetic (NOD mice) and diabetic animals submitted to antioxidant treatment and physical exercise. For histological analysis of the sebaceous glands, specific staining in histochemistry with sudan black and immunohistochemistry reaction with adipophilin were used in the evaluation. Statistical analysis showed significant proximity between the values of the control group and the diabetic group submitted to the swimming exercise (DS group) and similar values between the untreated diabetic group (UD group) and diabetic group treated with the antioxidant N-acetylcysteine (DNa group), which did not prevent possible differences where p < 0.01. Adipophilin (ADPH) immunohistochemistry permitted more intense lipid staining in SGs, the preservation of the SG in the control group, and a morphological deformed appearance in the UD and DNa groups. However, weak morphological recovery of the SG was observed in the DS-Na group, being more expressive in the DS group. In conclusion, the groups submitted to physical exercises showed better results in the recovery of the analyzed tissue, even being in the physiological conditions caused by spontaneous diabetes.

Association of Real-time Continuous Glucose Monitoring With Glycemic Control and Acute Metabolic Events Among Patients With Insulin-Treated Diabetes.

Importance: Continuous glucose monitoring (CGM) is recommended for patients with type 1 diabetes; observational evidence for CGM in patients with insulin-treated type 2 diabetes is lacking. Objective: To estimate clinical outcomes of real-time CGM initiation. Design, Setting, and Participants: Exploratory retrospective cohort study of changes in outcomes associated with real-time CGM initiation, estimated using a difference-in-differences analysis. A total of 41 753 participants with insulin-treated diabetes (5673 type 1; 36 080 type 2) receiving care from a Northern California integrated health care delivery system (2014-2019), being treated with insulin, self-monitoring their blood glucose levels, and having no prior CGM use were included. Exposures: Initiation vs noninitiation of real-time CGM (reference group). Main Outcomes and Measures: Ten end points measured during the 12 months before and 12 months after baseline: hemoglobin A1c (HbA1c); hypoglycemia (emergency department or hospital utilization); hyperglycemia (emergency department or hospital utilization); HbA1c levels lower than 7%, lower than 8%, and higher than 9%; 1 emergency department encounter or more for any reason; 1 hospitalization or more for any reason; and number of outpatient visits and telephone visits. Results: The real-time CGM initiators included 3806 patients (mean age, 42.4 years [SD, 19.9 years]; 51% female; 91% type 1, 9% type 2); the noninitiators included 37 947 patients (mean age, 63.4 years [SD, 13.4 years]; 49% female; 6% type 1, 94% type 2). The prebaseline mean HbA1c was lower among real-time CGM initiators than among noninitiators, but real-time CGM initiators had higher prebaseline rates of hypoglycemia and hyperglycemia. Mean HbA1c declined among real-time CGM initiators from 8.17% to 7.76% and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, -0.40%; 95% CI, -0.48% to -0.32%; P < .001). Hypoglycemia rates declined among real-time CGM initiators from 5.1% to 3.0% and increased among noninitiators from 1.9% to 2.3% (difference-in-differences estimate, -2.7%; 95% CI, -4.4% to -1.1%; P = .001). There were also statistically significant differences in the adjusted net changes in the proportion of patients with HbA1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; P < .001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2% to 16.1%; P < .001), and higher than 9% (adjusted difference-in-differences estimate, -7.1%; 95% CI, -9.5% to -4.6%; P < .001) and in the number of outpatient visits (adjusted difference-in-differences estimate, -0.4; 95% CI, -0.6 to -0.2; P < .001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; P < .001). Initiation of real-time CGM was not associated with statistically significant changes in rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason. Conclusions and Relevance: In this retrospective cohort study, insulin-treated patients with diabetes selected by physicians for real-time continuous glucose monitoring compared with noninitiators had significant improvements in hemoglobin A1c and reductions in emergency department visits and hospitalizations for hypoglycemia, but no significant change in emergency department visits or hospitalizations for hyperglycemia or for any reason. Because of the observational study design, findings may have been susceptible to selection bias.

Outpatient clinic-wide psychological screening for children and adolescents with type 1 diabetes in Qatar: An initiative for integrative healthcare in the Gulf region.

OBJECTIVE: To identify culturally appropriate psychological screening measures for children and adolescents with type 1 diabetes in Qatar, determine rates of depressive and anxiety symptoms in a clinical sample, and examine associations between screening measures, demographic variables, medical characteristics, and diabetes treatment outcomes, specifically HbA1c. METHODS: A total of 150 participants with type 1 diabetes aged 10-17 were recruited. Participants were Arabic or English speaking and of Qatari and non-Qatari nationality. Participants completed the Mood and Feelings Questionnaire (child and parent proxy form), the Spence Children's Anxiety Scale, and the Pediatric Quality of Life, Diabetes version (child and parent proxy form). Glycosylated hemoglobin (HbA1c) on the date of the testing was recorded. RESULTS: Approximately ten percent (10.2%) of children and adolescents scored above the cutoff score of 27 indicating clinically significant depressive symptoms, and 12.8% of parents rated their child above the respective cutoff score of 21 for the parent proxy form. Further, 36% of the sample reported clinically significant anxiety symptoms, scoring above the cutoff score of 50. Parent report on their child's quality of life predicted HbA1c (F[6, 140] = 5.42, p = 0.000); B = -0.05, p = 0.002). CONCLUSIONS: Rates of depressive and anxiety symptoms are comparable to those observed in western countries. Thus, systematic screening for depression and anxiety in children and adolescents with type 1 diabetes should be implemented in Qatar. This will help inform decisions to refer to mental health services and thus provide more integrated care, possibly improving treatment outcomes.

Understanding the Activation of Platelets in Diabetes and Its Modulation by Allyl Methyl Sulfide, an Active Metabolite of Garlic.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disorder associated with higher risk of having cardiovascular disease. Platelets play a promising role in the pathogenesis of cardiovascular complications in diabetes. Since last several decades, garlic and its bioactive components are extensively studied in diabetes and its complications. Our aim was to explore the antiplatelet property of allyl methyl sulfide (AMS) focusing on ameliorating platelet activation in diabetes. METHOD: We used streptozotocin- (STZ-) induced diabetic rats as model for type 1 diabetes. We have evaluated the effect of allyl methyl sulfide on platelet activation by administrating AMS to diabetic rats for 10 weeks. Flow cytometry-based analysis was used to evaluate the platelet activation, platelet aggregation, platelet macrophage interaction, and endogenous ROS generation in the platelets obtained from control, diabetes, and AMS- and aspirin-treated diabetic rats. RESULTS: AMS treatment for 10 weeks effectively reduced the blood glucose levels in diabetic rats. Three weeks of AMS (50 mg/kg/day) treatment did not reduce the activation of platelets but a significant (p < 0.05) decrease was observed after 10 weeks of treatment. Oral administration of AMS significantly (p < 0.05) reduced the baseline and also reduced ADP-induced aggregation of platelets after 3 and 10 weeks of treatment. Furthermore, 10 weeks of AMS treatment in diabetic rats attenuated the endogenous ROS content (p < 0.05) of platelets and platelet macrophage interactions. The inhibition of platelet activation in diabetic rats after AMS treatment was comparable with aspirin treatment (30 mg/kg/day). CONCLUSION: We observed an inhibitory effect of allyl methyl sulfide on platelet aggregation, platelet activation, platelet macrophage interaction, and increased ROS levels in type 1 diabetes. Our data suggests that AMS can be useful to control cardiovascular complication in diabetes via inhibition of platelet activation.

Insulin Resistance in Adults with Type 1 Diabetes is Associated with Lower Vitamin D Serum Concentration.

AIM: Type 1 diabetes mellitus (T1DM) is a disease characterized by an absolute deficiency of endogenous insulin secretion. Insulin resistance (IR) may develop among patients with T1DM. Vitamin D deficiency was reported to be a risk factor in the development of IR. The aim of the study was to assess the relationship between serum concentrations of 25-hydroxyvitamin D (25(OH)D) and IR among patients with T1DM. METHODS: The test group consisted of 110 adult patients [males=65 (59%)] with T1DM. Participants were recruited in Poland between 1st October and 30th April in 2015/2016 and 2016/2017. VD serum level was assessed by ELISA array. IR was assessed by estimated Glucose Disposal Rate (eGDR). RESULTS: In the study group 21 (19%) patients were recognized as IR according to eGDR cut-offs (<7.5 mg/kg/min), 52 (47.3%) patients had VD deficiency (25(OH)D<20 ng/ml), 16 (14.5%) patients had 25(OH)D<10 ng/ml. Only 6 (5%) participants reported VD supplementation. Patients with IR, according to eGDR cut-off revealed significantly lower 25(OH)D serum level 15.7 (9.2-28.4) vs. 22.1 (13.0-38.4) ng/ml; p=0.04 as compared to patients without IR. R Spearman analysis found a positive relationship between VD and eGDR (Rs=0.27; p<0.01). Logistic regression analysis revealed significant relationship between the presence of IR and VD serum level/presence of 25(OH)D serum level below 10 ng/ml, both models adjusted to sex, age, BMI, LDL and triglycerides, accordingly (OR=0.95, CI: 0.90-0.99; p=0.04) and (OR=4.19, CI: 1.04-16.93; p=0.04). CONCLUSION: The serum concentration of Vitamin D is negatively associated with insulin resistance in patients with T1DM and may have clinical implications.

Effects of mindfulness-based intervention on glycemic control and psychological outcomes in people with diabetes: A systematic review and meta-analysis.

AIMS/INTRODUCTION: Psychological therapies have showed benefits for both glycemic control and psychological outcomes in people with diabetes. However, the effects of mindfulness-based intervention (MBI) on glycemic control and psychological outcomes are inconsistent across studies, and the evidence for MBI has not been summarized. We aimed to identify the effects of MBI on glycemic control and psychological outcomes in people with diabetes by carrying out a systematic review and meta-analysis. MATERIALS AND METHODS: Six databases (Pubmed, Embase, CINAHL, Cochrane, Web of science and PsycINFO) were searched from inception to October 2019. Randomized controlled trials of MBI for people with type 1 and type 2 diabetes were included. Two authors independently extracted relevant data and assessed the risk of bias, with a third reviewer as arbitrator. Subgroup analyses and sensitivity analyses were also carried out. RESULTS: Eight studies with 841 participants met the eligibility criteria. Meta-analysis showed that MBI can slightly improve glycosylated hemoglobin (HbA1c; -0.25%, 95% confidence interval [CI] -0.43 to -0.07) and diabetes-related distress (-5.81, 95% CI -10.10 to -1.52) contribute to a moderate effect size in reducing depression (standardized mean difference -0.56, 95% CI -0.82 to -0.30) and stress (standardized mean difference -0.53, CI -0.75 to -0.31). Subgroup analyses showed greater HbA1c reductions in subgroups with baseline HbA1c levels <8% and follow-up duration >6 months. Mixed effects were observed for anxiety. CONCLUSIONS: MBI appears to have benefits on HbA1c, depression, stress and diabetes-related distress in people with diabetes. More rigorous studies with longer follow-up duration are warranted to establish the full potential of MBI.

Artificial Pancreas With Carbohydrate Suggestion Performance for Unannounced and Announced Exercise in Type 1 Diabetes.

OBJECTIVE: To evaluate the safety and performance of a new multivariable closed-loop (MCL) glucose controller with automatic carbohydrate recommendation during and after unannounced and announced exercise in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: A randomized, 3-arm, crossover clinical trial was conducted. Participants completed a heavy aerobic exercise session including three 15-minute sets on a cycle ergometer with 5 minutes rest in between. In a randomly determined order, we compared MCL control with unannounced (CLNA) and announced (CLA) exercise to open-loop therapy (OL). Adults with T1D, insulin pump users, and those with hemoglobin (Hb)A1c between 6.0% and 8.5% were eligible. We investigated glucose control during and 3 hours after exercise. RESULTS: Ten participants (aged 40.8 ± 7.0 years; HbA1c of 7.3 ± 0.8%) participated. The use of the MCL in both closed-loop arms decreased the time spent <70 mg/dL of sensor glucose (0.0%, [0.0-16.8] and 0.0%, [0.0-19.2] vs 16.2%, [0.0-26.0], (%, [percentile 10-90]) CLNA and CLA vs OL respectively; P = 0.047, P = 0.063) and the number of hypoglycemic events when compared with OL (CLNA 4 and CLA 3 vs OL 8; P = 0.218, P = 0.250). The use of the MCL system increased the proportion of time within 70 to 180 mg/dL (87.8%, [51.1-100] and 91.9%, [58.7-100] vs 81.1%, [65.4-87.0], (%, [percentile 10-90]) CLNA and CLA vs OL respectively; P = 0.227, P = 0.039). This was achieved with the administration of similar doses of insulin and a reduced amount of carbohydrates. CONCLUSIONS: The MCL with automatic carbohydrate recommendation performed well and was safe during and after both unannounced and announced exercise, maintaining glucose mostly within the target range and reducing the risk of hypoglycemia despite a reduced amount of carbohydrate intake.Register Clinicaltrials.gov: NCT03577158.

Puerarin ameliorates skeletal muscle wasting and fiber type transformation in STZ-induced type 1 diabetic rats.

Puerarin is an isoflavonoid extracted from Pueraria lobate with extensive pharmacological effects in traditional Chinese medicine. The evidence implicates that puerarin mitigates hyperglycemia and various relevant complications. Here, the effect of puerarin on skeletal muscle wasting induced by type 1 diabetes (T1D) was explored. Streptozotocin (STZ)-induced T1D male Sprague Dawley (SD) rats were used in this study. Muscle strength, weight and size were measured. L6 rat skeletal muscle cells were applied for in vitro study. Our results showed that eight-week oral puerarin administration (100 mg/kg) increased muscle strengths and weights accompanied by enhanced skeletal muscle cross-sectional areas in diabetic rats. Simultaneously, puerarin also reduced expressions of several muscle wasting marker genes including F-box only protein 32 (Atrogin-1) and muscle-specific RING-finger 1 (Murf-1) in diabetic group both in vitro and in vivo. Transformation from type I fibers (slow muscle) to type II fibers (fast muscle) were also observed under puerarin administration in diabetic rats. Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells. In conclusion, our study showed that puerarin mitigated skeletal muscle wasting in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition. Whether this effect in murine applies to humans remains to be determined.

The Protective Effects of Lupine (Lupinus albus) Fruit Extract Against to Destructive Effects of Hyperglycemia in Type I Diabetic Rats.

BACKGROUND: Lupinus albus is a member of the Fabaceae family. As a natural or cultivated plant, Lupinus albus is distributed in Europe, the Balkans and Turkey, especially in Marmara and Aegean regions. The lupine is a nutritious and protective plant against diabetes. OBJECTIVE: In the present study, the effects of Lupinus albus fruits on malondialdehyde (MDA), reduced glutathione (GSH), total protein, ADEK vitamins, and cholesterol values, which are the indicators of oxidative damage and antioxidant defense. In this regard, muscle, liver, renal, and brain tissues of STZ-induced type I diabetes rats were studied. METHODS: The analyzes of ADEK vitamins and cholesterol levels in tissues were performed via Shimadzu HPLC device. The lipid peroxidation levels were measured at 532 nm in spectrophotometer. Determination of GSH was read at 412 nm against blank, and for the total protein levels Lowry method was applied. RESULTS: According to the results obtained, it was determined that among the rats with induced type I diabetes, the group applied lupine fruit extract was found to have increased GSH level and decreased MDA levels in all the tissues. The protein values were increased in liver tissues but decreased in the other tissues. The level of vitamins was significantly increased in almost all the tissues in the diabetic group. CONCLUSION: In the present study, it was shown that the lupine reduced the devastating effects of type I diabetes by decreasing the fasting blood glucose and lipid peroxidation values and increasing the glutathione level in comparison to the diabetic group.

Omega-3 polyunsaturated fatty acid supplementation versus placebo on vascular health, glycaemic control, and metabolic parameters in people with type 1 diabetes: a randomised controlled preliminary trial.

BACKGROUND: The role of omega-3 polyunsaturated fatty acids (n-3PUFA), and the potential impact of n-3PUFA supplementation, in the treatment and management of type 1 diabetes (T1D) remains unclear and controversial. Therefore, this study aimed to examine the efficacy of daily high-dose-bolus n-3PUFA supplementation on vascular health, glycaemic control, and metabolic parameters in subjects with T1D. METHODS: Twenty-seven adults with T1D were recruited to a 6-month randomised, double-blind, placebo-controlled trial. Subjects received either 3.3 g/day of encapsulated n-3PUFA or encapsulated 3.0 g/day corn oil placebo (PLA) for 6-months, with follow-up at 9-months after 3-month washout. Erythrocyte fatty acid composition was determined via gas chromatography. Endpoints included inflammation-associated endothelial biomarkers (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], E-selectin, P-selectin, pentraxin-3, vascular endothelial growth factor [VEGF]), and their mediator tumor necrosis factor alpha [TNFα] analysed via immunoassay, vascular structure (carotid intima-media thickness [CIMT]) and function (brachial artery flow mediated dilation [FMD]) determined via ultrasound technique, blood pressure, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial metabolism. RESULTS: Twenty subjects completed the trial in full. In the n-3PUFA group, the mean ± SD baseline n-3PUFA index of 4.93 ± 0.94% increased to 7.67 ± 1.86% (P < 0.001) after 3-months, and 8.29 ± 1.45% (P < 0.001) after 6-months. Total exposure to n-3PUFA over the 6-months (area under the curve) was 14.27 ± 3.05% per month under n-3PUFA, and 9.11 ± 2.74% per month under PLA (P < 0.001). VCAM-1, ICAM-1, E-selectin, P-selectin, pentraxin-3, VEGF, TNFα, CIMT, FMD, blood pressure, HbA1c, FPG, and postprandial metabolism did not differ between or within groups after treatment (P > 0.05). CONCLUSIONS: This study indicates that daily high-dose-bolus of n-3PUFA supplementation for 6-months does not improve vascular health, glucose homeostasis, or metabolic parameters in subjects with T1D. The findings from this preliminary RCT do not support the use of therapeutic n-3PUFA supplementation in the treatment and management of T1D and its associated complications. Trial Registration ISRCTN, ISRCTN40811115. Registered 27 June 2017, http://www.isrctn.com/ISRCTN40811115 .

Association between Serum Vitamin D and Diabetic Retinopathy in Portuguese Patients with Type 1 Diabetes.

INTRODUCTION: Recently, vitamin D has gained importance as a diabetes risk modifier. Our aim was to assess the association between serum vitamin D levels and the prevalence of diabetic retinopathy in patients with type 1 diabetes. MATERIAL AND METHODS: Retrospective review of a population of patients with type 1 diabetes followed in a Portuguese tertiary center. Patients were included if they had an ophthalmological evaluation and a serum 25-hydroxyvitamin D level determination within the same year. Logistic regression analysis was used to adjust for possible confounders. RESULTS: We included 182 patients (47% male), and 57% (n = 103) had signs of diabetic retinopathy. We found a significant association between lower circulating levels of 25-hydroxyvitamin D levels and a greater prevalence of diabetic retinopathy after adjusting for confounders (duration of diabetes, estimated glomerular filtration rate, age, sex, metabolic control, season, dyslipidemia and hypertension) (OR = 0.94; 95% CI 0.90 - 0.99, p = 0.023). Longer duration of diabetes and worse metabolic control also remained associated with diabetic retinopathy in the multivariate analysis (OR = 1.20; 95% CI 1.13 - 1.27, p < 0.001 and OR = 4.13; 95% CI 1.34 - 12.7, p = 0.013, respectively). CONCLUSION: Lower levels of vitamin D were associated with an increased prevalence of diabetic retinopathy in patients with type 1 diabetes, after adjusting for possible confounders. Future controlled studies may elucidate the molecular routes for this association as well as the role of supplementation in the prevention of diabetes microvascular complications.

Introdução: A vitamina D tem vindo a ganhar importância como um modificador do risco de diabetes. O objetivo deste estudo foi avaliar a associação entre os níveis séricos de vitamina D e a prevalência de retinopatia diabética em pacientes com diabetes tipo 1. Material e Métodos: Estudo retrospetivo de uma população de doentes com diabetes tipo 1, seguidos num centro hospitalar terciário português. Os pacientes foram incluídos se tivessem uma avaliação oftalmológica e um doseamento dos níveis de 25-hidroxivitamina D no mesmo ano. Os ajustes para eventuais variáveis confundidoras foi realizado recorrendo a uma análise de regressão logística. Resultados: Foram incluídos 182 doentes (47% sexo masculino), dos quais 57% (n = 103) demonstravam sinais de retinopatia diabética. Foi encontrada uma associação significativa entre níveis inferiores de 25-hidroxivitamina D circulante sérica e uma maior prevalência de retinopatia diabética, depois do ajuste para os confundidores incluídos (duração da diabetes, taxa de filtração glomerular estimada, idade, sexo, controlo metabólico, estação do ano, dislipidemia e hipertensão) (OR = 0,94; 95% IC 0,90 - 0,99, p = 0,023). Uma maior duração da diabetes, assim como um pior controlo metabólico, mantiveram também uma associação significativa com uma maior prevalência de retinopatia diabética na análise multivariada (OR = 1,20; 95% IC 1,13 - 1,27, p < 0,001; OR = 4,13; 95% IC 1,34 - 12,7, p = 0,013, respetivamente). Conclusão: Níveis inferiores de vitamina D séricos demonstraram-se associados a uma prevalência superior de retinopatia diabética em pacientes com diabetes tipo 1, após o ajuste para eventuais variáveis confundidoras. Futuramente, estudos experimentais poderão estabelecer as vias moleculares implicadas nesta associação, assim como um papel concreto da suplementação na prevenção das complicações microvasculares da diabetes.

Allogenic Adipose Tissue-Derived Stromal/Stem Cells and Vitamin D Supplementation in Patients With Recent-Onset Type 1 Diabetes Mellitus: A 3-Month Follow-Up Pilot Study.

Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D. Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3). Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (-4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83). Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D. ClinicalTrials.gov registration: NCT03920397.

The application of metabolomics in investigating anti-diabetic activity of medicinal plants.

Diabetes mellitus is the most prevalent endocrine disease in the world and is likely to be the major epidemic in human history. In current years, many modern anti-diabetic medicines have been produced and introduced into the markets, however, long-term treatment of diabetes using synthetic drugs is limited. Medicinal plants play a great role in the treatment of diabetes. Many medicinal plants and their related traditional treatments for diabetes are used throughout the world and represent promising alternatives for the management of diabetes treatment. Metabolomics researches on diabetes have contributed to many aspects of exploring biomarkers and understanding the progression of the disease at metabolic levels. In addition, in the last decade, a number of metabolomics studies have focused on investigating the action mechanism of various herbal medicines. This paper aims to highlight and review a series of metabolomics studies that carried out on the role of herbal medicines on obesity and diabetes, finding potential biomarkers and also characterizing the metabolic disturbances associated with diabetes development. The findings showed that the metabolism of glycolysis/gluconeogenesis (glucose, pyruvate, lactate), TCA cycle (succinate, citrate, ß-hydroxybutyrate, 2-oxoglutarate), lipid metabolism (acetoacetate, acetate) and amino acid metabolic pathways (valine, leucine, and isoleucine, hippurate, creatine) were more significantly disturbed metabolic pathways and biomarkers in diabetic models and herbal medicines affect these metabolic pathways by different mechanisms.

Relaxation training significantly reduced blood glucose levels in patients with type 1 diabetes mellitus.

PURPOSE/OBJECTIVE: The present study was designed to test whether adding a relaxation training technique to the medical treatment of patients with type 1 diabetes mellitus could, adjusting for the non-specific factors of therapy, lead to an improvement in the patients' condition. METHOD: Forty-six participants were randomly allocated either to an experimental (intervention) group, receiving weekly sessions of relaxation training, or to a control group (placebo) receiving weekly blood circulation training exercises. Measures included the State and Trait Anxiety Inventory, blood glucose levels, high-density lipoprotein levels, cholesterol levels, body weight, HbA1c levels, the Mood Adjective Checklist (MACL), a diary checklist, and urine glucose levels. Assessment of psychological and physiological parameters was conducted before and upon completion of the intervention (8 weeks). RESULTS: Trait anxiety and the main metabolic measurement of blood glucose levels and HbA1C revealed significant differences over time, predominantly among patients in the intervention group. CONCLUSIONS: Relaxation techniques as an adjunct to medical treatment are a useful tool for patients with type 1 diabetes mellitus.

How Do the Challenges of Emerging Adulthood Inform our Understanding of Diabetes Distress? An Integrative Review.

PURPOSE OF REVIEW: Emerging adulthood (ages 18-29) presents many emotional, social, and developmental challenges that can contribute to an increased sense of burden when managing type 1 diabetes (T1D). Diabetes distress (DD) is the concept that captures the emotional burden, frustrations, and worries resulting from living with T1D. This integrative review sets out to examine the impact of developmental context by answering this question: How do the challenges of emerging adulthood inform our understanding of DD? RECENT FINDINGS: DD is highly prevalent in emerging adults and occurs at higher rates than in other age groups. Qualitative studies reveal that DD is embedded within the developmental challenges specific to living with T1D during this stage. Quantitative studies reveal the prevalence and correlates of DD in this age group, and qualitative studies augment these findings by capturing the scope and complexity of the emotional burden of living with T1D as an emerging adult.

Diabetes Healthcare Professionals Use Multiple Continuous Glucose Monitoring Data Indicators to Assess Glucose Management.

BACKGROUND: Continuous glucose monitoring (CGM) offers multiple data features that can be leveraged to assess glucose management. However, how diabetes healthcare professionals (HCPs) actually assess CGM data and the extent to which they agree in assessing glycemic management are not well understood. METHODS: We asked HCPs to assess ten de-identified CGM datasets (each spanning seven days) and rank order each day by relative glycemic management (from "best" to "worst"). We also asked HCPs to endorse features of CGM data that were important in making such assessments. RESULTS: In the study, 57 HCPs (29 endocrinologists; 28 diabetes educators) participated. Hypoglycemia and glycemic variance were endorsed by nearly all HCPs to be important (91% and 88%, respectively). Time in range and daily lows and highs were endorsed more frequently by educators (all Ps < .05). On average, HCPs endorsed 3.7 of eight data features. Overall, HCPs demonstrated agreement in ranking days by relative glycemic control (Kendall's W = .52, P < .001). Rankings were similar between endocrinologists and educators (R2 = .90, Cohen's kappa = .95, mean absolute error = .4 [all Ps < .05]; Mann-Whitney U = 41, P = .53). CONCLUSIONS: Consensus in the endorsement of certain data features and agreement in assessing glycemic management were observed. While some practice-specific differences in feature endorsement were found, no differences between educators and endocrinologists were observed in assessing glycemic management. Overall, HCPs tended to consider CGM data holistically, in alignment with published recommendations, and made converging assessments regardless of practice.

Diabetes-specific formulas high in monounsaturated fatty acids and metabolic outcomes in patients with diabetes or hyperglycaemia. A systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to compare the metabolic benefits of diabetes-specific formulas (DSF) high in monounsaturated fatty acids (MUFA) with standard formulas (STDF) in adult patients with type 1, type 2 diabetes or stress-induced hyperglycaemia. RESEARCH DESIGN AND METHODS: A systematic review and meta-analysis were conducted through a literature search using different electronic databases from the index date to December 2018. We included randomised controlled trials that assessed the health benefits of high MUFA DSF vs STDF. Included outcomes were glycaemic control, lipid metabolism and tolerance. Effect sizes were calculated as standardised mean differences (SMDs) (<0.4 were considered small, 0.4-0.7 moderate and >0.7 large). This systematic review was registered as CRD42018108931 on Prospero. RESULTS: Of 385 references reviewed, 18 studies involving 845 adults met our inclusion criteria and contributed to the meta-analysis. Use of a high MUFA DSF compared with a STDF was associated with a statistically significant decrease in peak of postprandial glucose [SMD -1.53, 95% confidence interval (CI) -2.44 to -0.61], incremental glucose response (SMD -1.19, 95% CI -1.71 to -0.68), area under the curve of plasma insulin (SMD -0.65, 95% CI -1.03 to -0.26), mean blood glucose level (SMD -0.41, 95% CI -0.63 to -0.19), glycosylated haemoglobin (HbA1c) change (SMD -0.63, 95% CI -1.21 to -0.05), glucose variability (SMD -0.93, -1.55 to -0.31), mean administered insulin dose (SMD -0.49, 95% CI -0.85 to -0.14), mean blood triglycerides (SMD -0.34, 95% CI -0.65 to -0.03) and increase of mean blood high-density lipoproteins (SMD +0.42, 95% CI 0.08 to 0.76). Non-significant differences were found for tolerance [odds ratio (OR) 0.95, 95% CI 0.87 to 1.05]. CONCLUSIONS: This meta-analysis shows that a DSF (oral supplements and tube feeds) high in MUFAs can improve glucose control and metabolic risk factors among patients with diabetes or stress-induced hyperglycaemia compared with a STDF.