People with type 1 diabetes exhibit lower exercise capacity compared to a control population with similar physical activity levels.

AIMS: We aimed to assess physical activity (PA) levels, adherence to PA guidelines, and fitness capacity in individuals with type 1 diabetes (T1D) and control population. METHODS: This cross-sectional study included 232 T1D and 248 controls. PA levels (IPAQ-SF questionnaire), adherence to guidelines (>150 min/week of moderate-to-vigorous PA), fitness capacity (VO2max, maximal incremental test on a cycle ergometer and 1RM test) were assessed, along with other clinical variables. RESULTS: Total PA levels (T1D 2202 ± 1839 vs. controls 2357 ± 2189 METs/min/week), adherence (T1D 53.1 % vs controls 53.2 %), and sedentariness (T1D 27.3 % vs. controls 25.1 %) were similar between groups. However, participants with T1D exhibited significantly lower levels of VO2max (29.1 ± 10.5 vs. 32.5 ± 11.5 mlO2/kg/min, p < 0.001), work capacity (2.73 ± 1.03 vs. 3 ± 10 W/kg of body weight, p = 0.004) and strength capacity (2.29 ± 0.53 vs. 2.41 ± 0.79 kg/kg body weight in 1RM, p = 0.01) than controls, after adjusting for sex and age. CONCLUSIONS: Individuals with T1D exhibit lower fitness capacity compared to a control population, regardless of age and sex, even when presenting similar levels of total physical activity and adherence to guidelines.

Changes in physical activity habits in subjects with type 1 diabetes: A comparative study 10 years apart.

INTRODUCTION: Physical activity (PA) is highly recommended in type 1 diabetes (T1D). Few studies have reported the amount of PA performed by individuals with T1D in their daily life, and there is no information about changes over time. MATERIAL AND METHODS: Cross-sectional study in patients with T1D from a referral hospital recruited in two different periods: data from the Biobank registers from 2009 and data from patients attending visits at the hospital in 2019, on a consecutive basis. Data included clinical characteristics and the PA assessment through the International Physical Activity Questionnaire-short form (IPAQ-SF). RESULTS: In 2019, participants with T1D (n=135) reported a lower sedentary lifestyle and greater levels of high PA compared to subjects with T1D (n=355) from 10 years earlier (6.7% vs. 14.1% sedentariness, p=0.015; and 52.6% vs. 25.4% of high PA, p<0.001, respectively). Similar results were identified when the groups were divided according to sex. Both groups presented similar distribution by sex (women, 54% vs. 55%), age (40 vs. 39 years old), years with diabetes (20 vs. 18 years), BMI (25 vs. 24kg/m2) and glycated haemoglobin (7.5% vs. 7.5%, respectively; p>0.05 for all comparisons). Sex and age groups were not determinant for sedentary lifestyle in the different years studied. Analysing all the 490 participants, there was an inverse correlation of age with sitting hours (p=0.024, r=-0.102), total METs (p<0.001, r=-0.146) and HbA1c (p=0.038, r=-0.097). No correlations were found between PA and HbA1c or BMI. CONCLUSIONS: The findings indicate that PA has significantly increased in subjects with T1D over the last 10 years. Future studies are needed to assess whether these healthier habits translate into better outcomes in this high-risk population.

High Intensity Interval Training reduces hypoglycemic events compared with continuous aerobic training in individuals with type 1 diabetes: HIIT and hypoglycemia in type 1 diabetes.

AIMS: to investigate if a High Intensity Interval Training (HIIT) protocol improves glycemic control and fitness capacity, compared to traditional moderate Intensity Continuous Training (MICT) exercise. METHODS: 30 sedentary individuals with type 1 diabetes (T1D) and 26 healthy controls were assigned to a 3-week HIIT or MICT protocol. Blood glucose levels by continuous glucose monitoring system and fitness status were compared before and after the study period. RESULTS: During workouts, blood glucose levels remained stable in HIIT exercise (+3.2 ± 16.2 mg/dl (p = 0.43)), while decreased in MICT (-27.1 ± 17.5 mg/dl (p < 0.0001)) exercise. In addition, out of the 9 training sessions, HIIT volunteers needed to take carbohydrate supplements to avoid hypoglycemia in 0.56 ± 0.9 sessions, compared to 1.83 ± 0.5 sessions (p < 0.04) in MICT individuals. In the analysis of blood glucose levels between rest and training days (24h-period), training significantly reduced mean glycemic levels in both groups, but the MICT exercise results in an increase in the frequency of hypoglycemic episodes. The response to exercise seems to be attenuated in individuals with T1D, especially in HIIT group. CONCLUSION: HIIT training results in a greater glycemic stability, with reduction of hypoglycemic episodes.

Ammonium quantification in human plasma by proton nuclear magnetic resonance for staging of liver fibrosis in alcohol-related liver disease and nonalcoholic fatty liver disease.

Liver fibrosis staging is a key element driving the prognosis of patients with chronic liver disease. Currently, biopsy is the only technique capable of diagnosing liver fibrosis in patients with alcohol-related liver disease (ArLD) and nonalcoholic fatty liver disease (NAFLD) unequivocally. Noninvasive (e.g. plasma-based) biomarker assays are attractive tools to diagnose and stage disease, yet must prove that they are reliable and sensitive to be used clinically. Here, we demonstrate proton nuclear magnetic resonance as a method to rapidly quantify the endogenous concentration of ammonium ions from human plasma extracts and show their ability to report upon early and advanced stages of ArLD and NAFLD. We show that, irrespective of the disease etiology, ammonium concentration is a more robust and informative marker of fibrosis stage than current clinically assessed blood hepatic biomarkers. Subject to validation in larger cohorts, the study indicates that the method can provide accurate and rapid staging of ArLD and NAFLD without the need for an invasive biopsy.

Muscular carnosine is a marker for cardiorespiratory fitness and cardiometabolic risk factors in men with type 1 diabetes.

PURPOSE: Muscle is an essential organ for glucose metabolism and can be influenced by metabolic disorders and physical activity. Elevated muscle carnosine levels have been associated with insulin resistance and cardiometabolic risk factors. Little is known about muscle carnosine in type 1 diabetes (T1D) and how it is influenced by physical activity. The aim of this study was to characterize muscle carnosine in vivo by proton magnetic resonance spectroscopy (1H MRS) and evaluate the relationship with physical activity, clinical characteristics and lipoprotein subfractions. METHODS: 16 men with T1D (10 athletes/6 sedentary) and 14 controls without diabetes (9/5) were included. Body composition by DXA, cardiorespiratory capacity (VO2peak) and serum lipoprotein profile by proton nuclear magnetic resonance (1H NMR) were obtained. Muscle carnosine scaled to water (carnosineW) and to creatine (carnosineCR), creatine and intramyocellular lipids (IMCL) were quantified in vivo using 1H MRS in a 3T MR scanner in soleus muscle. RESULTS: Subjects with T1D presented higher carnosine CR levels compared to controls. T1D patients with a lower VO2peak presented higher carnosineCR levels compared to sedentary controls, but both T1D and control groups presented similar levels of carnosineCR at high VO2peak levels. CarnosineW followed the same trend. Integrated correlation networks in T1D demonstrated that carnosineW and carnosineCR were associated with cardiometabolic risk factors including total and abdominal fat, pro-atherogenic lipoproteins (very low-density lipoprotein subfractions), low VO2peak, and IMCL. CONCLUSIONS: Elevated muscle carnosine levels in persons with T1D and their effect on atherogenic lipoproteins can be modulated by physical activity.

Differences in Physiological Responses to Cardiopulmonary Exercise Testing in Adults With and Without Type 1 Diabetes: A Pooled Analysis.

OBJECTIVE: To investigate physiological responses to cardiopulmonary exercise (CPX) testing in adults with type 1 diabetes compared with age-, sex-, and BMI-matched control participants without type 1 diabetes. RESEARCH DESIGN AND METHODS: We compared results from CPX tests on a cycle ergometer in individuals with type 1 diabetes and control participants without type 1 diabetes. Parameters were peak and threshold variables of VO2, heart rate, and power output. Differences between groups were investigated through restricted maximum likelihood modeling and post hoc tests. Differences between groups were explained by stepwise linear regressions (P < 0.05). RESULTS: Among 303 individuals with type 1 diabetes (age 33 [interquartile range 22; 43] years, 93 females, BMI 23.6 [22; 26] kg/m2, HbA1c 6.9% [6.2; 7.7%] [52 (44; 61) mmol/mol]), VO2peak (32.55 [26.49; 38.72] vs. 42.67 ± 10.44 mL/kg/min), peak heart rate (179 [170; 187] vs. 184 [175; 191] beats/min), and peak power (216 [171; 253] vs. 245 [200; 300] W) were lower compared with 308 control participants without type 1 diabetes (all P < 0.001). Individuals with type 1 diabetes displayed an impaired degree and direction of the heart rate-to-performance curve compared with control participants without type 1 diabetes (0.07 [-0.75; 1.09] vs. 0.66 [-0.28; 1.45]; P < 0.001). None of the exercise physiological responses were associated with HbA1c in individuals with type 1 diabetes. CONCLUSIONS: Individuals with type 1 diabetes show altered responses to CPX testing, which cannot be explained by HbA1c. Intriguingly, the participants in our cohort were people with recent-onset type 1 diabetes; heart rate dynamics were altered during CPX testing.

Comparison of the diagnostic accuracy of diffusion-weighted and dynamic contrast-enhanced MRI with 18F-FDG PET/CT to differentiate osteomyelitis from Charcot neuro-osteoarthropathy in diabetic foot.

PURPOSE: To compare the diagnostic accuracy of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) involving two region of interest (ROI) sizes with 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to differentiate diabetic foot osteomyelitis (DFO) from Charcot neuro-osteoarthropathy (CN). METHOD: Thirty-one diabetic patients were included in this prospective study. Two readers independently evaluated DWI (apparent diffusion coefficient [ADC] and high-b-value signal pathological-to-normal bone ratio [DWIr]) and DCE-MRI parameters (Ktrans, Kep, Ve, internal area under the gadolinium curve at 60 s [iAUC60] and time intensity curve [TIC]) using two different ROI sizes, and 18F-FDG PET/CT parameters (visual assessment, SUVmax, delayed SUVmax, and percentage changes between SUVmax and delayed SUVmax). Techniques were compared by univariate analysis using the area under the receiver operating characteristic curve [AUC]. Reliability was analyzed with Kappa and Intraclass correlation [ICC]. RESULTS: DWIr, Ktrans and iAUC60 showed better diagnostic accuracy (AUC = 0.814-0.830) and reliability (ICC > 0.9) for large than for small ROIs (AUC = 0.736-0.750; ICC = 0.6 in Ktrans, 0.8 in DWIr and iAUC60). TIC showed moderate diagnostic performance (AUC = 0.739-0.761) and reliability (κ 0.7). Visual assessment of 18F-FDG PET/CT demonstrated a significantly higher accuracy (AUC = 0.924) than MRI parameters. Semi-quantitative 18F-FDG PET/CT parameters did not provide significant improvement over visual analysis (AUC = 0.848-0.903). CONCLUSION: DWIr, Ktrans and iAUC60 allowed reliable differentiation of DFO and CN, particularly for large ROIs. Visual assessment of 18F-FDG PET/CT was the most accurate technique for differentiation.

Management of Hypoglycemia in Adults with Type 1 Diabetes in Real-Life Condition.

INTRODUCTION: Hypoglycemia is the most common acute complication in individuals with type 1 diabetes (T1D). Episodes of mild or moderate hypoglycemia should be treated in adults with a dose of around 15-20 g fast-acting carbohydrates. However, this self-treatment of hypoglycemia in real-life condition is not well documented. OBJECTIVE: The aim of this study wasto determine the characteristics of hypoglycemia treatment in adults with T1D in a prospective study design. METHODS: Individuals with T1D were advised to record information related to hypoglycemia episodes for a period of 14 days. Quantity and quality (including glycemic index [GI] and glycemic load) of carbohydrates consumed in every hypoglycemia episode and others factors related with hypoglycemia such as physical activity, fear of hypoglycemia, or hypoglycemia awareness were analyzed. RESULTS: A total of 93 individuals (36.5 ± 16.2 years old, BMI of 24.9 ± 3.8 kg/m2, diabetes duration of 14.9 ± 10.4 years, and HbA1c levels of 7.3 ± 0.8%) were included in the study. A total of 483 episodes of mild or moderate hypoglycemia were reported, which supposed on average 2.7 ± 2.0 episodes a week. The quantity of carbohydrates consumed in all episodes of hypoglycemia was 25.9 ± 9.2 g. GI of food consumed in all episodes of hypoglycemia was classified as low (53.9 ± 8.3). Overtreatment of hypoglycemia, defined as ingestion of more than 20 g of carbohydrates, occurred in 50.3% of hypoglycemic episodes; even 22.3% of these episodes were treated with more than 30 g of carbohydrates. Fruit juice was the most popular option, chosen in almost 70% of the events. In addition, we observed other moderate or low GI foods such as milk, bread, cookies, and bakery products among the most consumed foods. CONCLUSION: A majority of the studied individuals with T1D does not manage hypoglycemia according to current American Diabetes Association guidelines, in most cases by overtreating, choosing foods with low glycemic effect, and not varying the dose of carbohydrates, depending on the physical activity performed.

Clinical characteristics, complications and management of patients with type 2 diabetes with and without diabetic kidney disease (DKD): A comparison of data from a clinical database.

BACKGROUND AND OBJECTIVES: The main objective of this study was to assess the percentage of co-morbid nephropathy in type 2 diabetes patients using the CKD-EPI equation and to compare the clinical characteristics and treatments of patients with type 2 diabetes with nephropathy with those of patients without nephropathy PATIENTS AND METHODS: This was a cross-sectional analysis of the demographic and clinical data registered in the IDIBAPS Biobank database. Patients were considered to have nephropathy if the diagnosis was reported in their clinical history, albuminuria (>30 mg/g) was indicated as present in the last urine test available, or an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 was calculated using the CKD-EPI equation. RESULTS: Clinical data were obtained from 1,397 patients with a diagnosis of type 2 diabetes. The percentage of patients with nephropathy was 29.3% (N= 369) (95% confidence interval, 26.8% to 31.9%); however, only 109 (7.8%) patients had a nephropathy diagnosis reported in their clinical history. Compared with patients without nephropathy, patients with nephropathy have a higher mean age, higher frequency of diabetes complications and received insulin more frequently. CONCLUSION: Our results show that the percentage of type 2 diabetes patients with nephropathy was high and that this comorbidity was associated with a significantly higher frequency of diabetes macro- and microvascular complications (compared to diabetes patients without DKD).

Low Physical Activity and Its Association with Diabetes and Other Cardiovascular Risk Factors: A Nationwide, Population-Based Study.

Low physical activity (PA), or sedentary lifestyle, is associated with the development of several chronic diseases. We aimed to investigate current prevalence of sedentariness and its association with diabetes and other cardiovascular risk factors. PA was evaluated in a population-based, cross-sectional, randomly sampled study conducted in 2009-2010 in Spain. International Physical Activity Questionnaire (SF-IPAQ) was used to assess PA. 4991 individuals (median age 50 years, 57% women) were studied. Prevalence of sedentariness was 32.3% for men and 39% for women (p < 0.0001). Sex differences were particularly notable (age*sex interaction, p = 0.0024) at early and older ages. Sedentary individuals had higher BMI (28 vs. 27 kg/m2) and obesity prevalence (37 vs. 26%). Low PA was present in 44, 43, and 38% of individuals with known diabetes (KDM), prediabetes/unknown-diabetes (PREDM/UKDM), and normal glucose regulation (p = 0.0014), respectively. No difference between KDM and PREDM/UKDM (p = 0.72) was found. Variables independently associated (p < 0.05) with sedentariness were age, sex, BMI, central obesity, Mediterranean diet adherence, smoking habit, HDL-cholesterol, triglycerides and dyslipidemia. Low PA is on the rise in Spain, especially among women. Sedentariness is associated with several cardiovascular risk factors and may be responsible for the increasing prevalence of obesity and diabetes in this country.

Improving Assessment of Lipoprotein Profile in Type 1 Diabetes by 1H NMR Spectroscopy.

Patients with type 1 diabetes (T1D) present increased risk of cardiovascular disease (CVD). The aim of this study is to improve the assessment of lipoprotein profile in patients with T1D by using a robust developed method 1H nuclear magnetic resonance spectroscopy (1H NMR), for further correlation with clinical factors associated to CVD. Thirty patients with T1D and 30 non-diabetes control (CT) subjects, matched for gender, age, body composition (DXA, BMI, waist/hip ratio), regular physical activity levels and cardiorespiratory capacity (VO2peak), were analyzed. Dietary records and routine lipids were assessed. Serum lipoprotein particle subfractions, particle sizes, and cholesterol and triglycerides subfractions were analyzed by 1H NMR. It was evidenced that subjects with T1D presented lower concentrations of small LDL cholesterol, medium VLDL particles, large VLDL triglycerides, and total triglycerides as compared to CT subjects. Women with T1D presented a positive association with HDL size (p<0.005; R = 0.601) and large HDL triglycerides (p<0.005; R = 0.534) and negative (p<0.005; R = -0.586) to small HDL triglycerides. Body fat composition represented an important factor independently of normal BMI, with large LDL particles presenting a positive correlation to total body fat (p<0.005; R = 0.505), and total LDL cholesterol and small LDL cholesterol a positive correlation (p<0.005; R = 0.502 and R = 0.552, respectively) to abdominal fat in T1D subjects; meanwhile, in CT subjects, body fat composition was mainly associated to HDL subclasses. VO2peak was negatively associated (p<0.005; R = -0.520) to large LDL-particles only in the group of patients with T1D. In conclusion, patients with T1D with adequate glycemic control and BMI and without chronic complications presented a more favourable lipoprotein profile as compared to control counterparts. In addition, slight alterations in BMI and/or body fat composition showed to be relevant to provoking alterations in lipoproteins profiles. Finally, body fat composition appears to be a determinant for cardioprotector lipoprotein profile.

Circulating miR-192 and miR-193b are markers of prediabetes and are modulated by an exercise intervention.

CONTEXT: Diabetes is frequently diagnosed late, when the development of complications is almost inevitable, decreasing the quality of life of patients. However, early detection of affected individuals would allow the implementation of timely and effective therapies. OBJECTIVE: Here we set to describe the profile of circulating microRNAs (miRNAs) in prediabetic patients with the intention of identifying novel diagnostic and therapeutic tools. DESIGN: We used real-time RT-PCR to measure the abundance of 176 miRNAs in serum of a cohort of 92 control and prediabetic individuals with either impaired fasting glucose or impaired glucose tolerance, as well as newly diagnosed diabetic patients. We validated the results in a second cohort of control and prediabetic subjects undergoing a therapeutic exercise intervention, as well as in a mouse model of glucose intolerance. RESULTS: We identified two miRNAs, miR-192 and miR-193b, whose abundance is significantly increased in the prediabetic state but not in diabetic patients. Strikingly, these miRNAs are also increased in plasma of glucose-intolerant mice. Moreover, circulating levels of miR-192 and miR-193b return to baseline in both prediabetic humans and glucose-intolerant mice undergoing a therapeutic intervention consisting in chronic exercise, which succeeded in normalizing metabolic parameters. CONCLUSIONS: Our data show that the pattern of circulating miRNAs is modified by defects in glucose metabolism in a similar manner in mice and humans. This circulating miRNA signature for prediabetes could be used as a new diagnostic tool, as well as to monitor response to intervention.

Metabolomics approach for analyzing the effects of exercise in subjects with type 1 diabetes mellitus.

The beneficial effects of exercise in patients with type 1 diabetes (T1D) are not fully proven, given that it may occasionally induce acute metabolic disturbances. Indeed, the metabolic disturbances associated with sustained exercise may lead to worsening control unless great care is taken to adjust carbohydrate intake and insulin dosage. In this work, pre- and post-exercise metabolites were analyzed using a (1)H-NMR and GC-MS untargeted metabolomics approach assayed in serum. We studied ten men with T1D and eleven controls matched for age, body mass index, body fat composition, and cardiorespiratory capacity, participated in the study. The participants performed 30 minutes of exercise on a cycle-ergometer at 80% VO(2)max. In response to exercise, both groups had increased concentrations of gluconeogenic precursors (alanine and lactate) and tricarboxylic acid cycle intermediates (citrate, malate, fumarate and succinate). The T1D group, however, showed attenuation in the response of these metabolites to exercise. Conversely to T1D, the control group also presented increases in α-ketoglutarate, alpha-ketoisocaproic acid, and lipolysis products (glycerol and oleic and linoleic acids), as well as a reduction in branched chain amino acids (valine and leucine) determinations. The T1D patients presented a blunted metabolic response to acute exercise as compared to controls. This attenuated response may interfere in the healthy performance or fitness of T1D patients, something that further studies should elucidate.

Biotesiometria: avaliaçäo do pé diabético em risco / Biothesiometry: evaluation of diabetic foot at risk

Os autores fazem uma revisäo crítica a respeito da biotesiometria, método de quantificaçäo da sensibilidade vibratória capaz de detectar pacientes diabéticos com alto risco de desenvolver úlceras nos pés. Säo discutidos neste artigo o princípio e técnicas utilizadas para avaliar a sensibilidade vibratória pelo biotesiômetro, suas vantagens e limitaçöes, bem como sua futura aplicaçäo na prática clínica diária com o objetivo de caracterizar a neuropatia periférica de pacientes com diabetes melito

Modelo experimental de induçäo de endometriose em ratas / Experimental model of endometriosis induction in rats

RETROSPECTIVA: A endometriose é uma doença nao completamente entendida, constituindo uma área da ginecologia na qual há grande atividade científica. Seria importante para facilitar o estudo dessa moléstia a existência de um modelo experimental de fácil obtençao e com baixo custo. OBJETIVOS: Descrever um modelo de endometriose induzida experimentalmente em ratas que permite a posterior avaliaçao macroscópica, microscópica e bioquímica da patologia. MATERIAIS E MÉTODOS: Foram utilizadas 30 ratas Wistar divididas em dois grupos: 18 animais foram submetidos à laparotomia na qual uma porçao do corno uterino esquerdo foi aberto longitudinalmente até atingir-se a cavidade endometrial, sendo o endométrio manipulado e implantado no peritônio; 12 ratas-controle sofreram apenas laparotomia sem manipulaçao do útero. Sessenta dias após o procedimento, as ratas foram re-operadas para avaliaçao macroscópica dos focos de endometriose e coleta de material para análise microscópica e citológica.RESULTADOS: Dentre as ratas que sofreram abertura uterina e sobreviveram, 84 por cento apresentavam focos macroscópicos de endometriose à re-intervençao. Nenhuma rata do grupo controle apresentou a doença.