Better Cardiorespiratory Fitness Defined as VO2max Increases the Chance of Partial Clinical Remission and Prolongs Remission Duration in People with Newly Diagnosed Type 1 Diabetes.

Introduction: An essential process affecting the course of type 1 diabetes (DM1) is the appearance and duration of clinical remission. One of the most important factors promoting the occurrence of remission is physical activity, due to increased activity of antioxidants, reduces insulin resistance and improves glucose transport. Maximal oxygen capacity (VO2max) is an objective measure of the body's aerobic capacity. To assess VO2max, oxygen uptake should be measured directly during the exercise test. The aim of the study was to evaluate the physical capacity in adults with DM1 and its relationship with the occurrence of partial clinical remission (pCR) during 2 years follow-up. Methods: The pCR was assessed by the following mathematical formula: A1c (%) + [4 × insulin dose (U/kg/d)]. The result ⩽9 indicates pCR. VO2max was assessed between 6th and 24th month of diabetes duration using an ergospirometer (COSMED K5 System), during an exercise test carried out on a cycloergometer (RAMP incremental exercise test). Results: The study group consisted of 32 adults with DM1. People with pCR were proved to have higher VO2max level [36.0 (33.0-41.5) vs 30.9 (26.5-34.4) ml/min/kg, P = .009. Univariate and multivariate regression confirmed a significant association between VO2max and presence of pCR [AOR 1.26 (1.05-1.52), P = .015]. Duration of remission was longer among group with higher VO2max results [15 (9-24) vs 9 (0-12) months, P = .043]. The positive relationship was observed between diabetes duration and VO2max (rs = 0.484, P = .005). Multivariate linear regression confirms a significant association between remission duration and VO2max (ml/min/kg) (ß = 0.595, P = .002). Conclusion: The higher VO2max, the better chance of partial clinical remission at 2 years of DM1 and longer duration of remission.

Better cardiorespiratory fitness increases the chance of partial clinical remission and prolongs remission duration in people with newly diagnosed type 1 diabetes. Introduction An essential process affecting the course of type 1 diabetes (DM1) is the appearance and duration of clinical remission. One of the most important factors promoting the occurrence of remission is physical activity, due to increased activity of antioxidants, reduces insulin resistance and improves glucose transport. Maximal oxygen capacity (VO₂max) is an objective measure of the body's aerobic capacity. To assess VO₂max, oxygen uptake should be measured directly during the exercise test. The aim of the study was to evaluate the physical capacity in adults with DM1 and its relationship with the occurrence of partial clinical remission (pCR) during 2 years follow-up. Methods The pCR was assessed by the following mathematical formula: A1c (%) + [4 × insulin dose (U/kg/d)]. The result ⩽9 indicates pCR. VO₂max was assessed between 6th and 24th month of diabetes duration using an ergospirometer (COSMED K5 System), during an exercise test carried out on a cycloergometer (RAMP incremental exercise test). Results The study group consisted of 32 adults with DM1. People with pCR were proved to have higher VO₂max level [36.0 (33.0-41.5) vs 30.9 (26.5-34.4) ml/min/kg, P = .009. Univariate and multivariate regression confirmed a significant association between VO₂max and presence of pCR [AOR 1.26 (1.05-1.52), P = .015]. Duration of remission was longer among group with higher VO₂max results [15 (9-24) vs 9 (0-12) months, P = .043]. The positive relationship was observed between diabetes duration and VO₂max (rs = 0.484, P = .005). Multivariate linear regression confirms a significant association between remission duration and VO₂max (ml/min/kg) (ß = 0.595, P = .002). Conclusions The higher VO₂max, the better chance of partial clinical remission at 2 years of DM1 and longer duration of remission.

Interactive calculator to estimate insulin sensitivity in type 1 diabetes.

The gold standard for measuring insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp, a time, costly, and labor-intensive research tool. A low insulin sensitivity is associated with a complication-risk in type 1 diabetes. Various formulae using clinical data have been developed and correlated with measured IS in type 1 diabetes. We consolidated multiple formulae into an online calculator (bit.ly/estimated-GDR), enabling comparison of IS and its probability of IS <4.45 mg/kg/min (low) or >6.50 mg/kg/min (high), as measured in a validation set of clamps in 104 adults with type 1 diabetes. Insulin sensitivity calculations using different formulae varied significantly, with correlations (R2) ranging 0.005-0.87 with agreement in detecting low and high glucose disposal rates in the range 49-93% and 89-100%, respectively. We demonstrate that although the calculated IS varies between formulae, their interpretation remains consistent. Our free online calculator offers a user-friendly tool for individual IS calculations and also offers efficient batch processing of data for research.

Lower air ozone concentration is associated with clinical remission in type 1 diabetes diagnosed in adulthood: a prospective, observational study in Wielkopolska region, Poland.

INTRODUCTION: Clinical remission in type 1 diabetes (T1D) results from metabolic compensation after insulin implementation and is caused by various factors. OBJECTIVES: Our aim was to investigate an association between air pollution defined based on ozone concentration in the month of T1D diagnosis and the early course of the disease, that is, glucose metabolism and the occurrence of remission. PATIENTS AND METHODS: This prospective, observational analysis included 96 adult patients with newly diagnosed T1D. The study group was divided according to the occurrence of remission at 12 months after the diagnosis. The levels of ambient ozone measured within the month of T1D diagnosis were calculated using the official data of Poland's Chief Inspectorate of Environmental Protection. Remission was defined according to the following formula: actual glycated hemoglobin (HbA1c)(%) level + [4 × insulin dose (units/kg per 24 h)] - value defining partial remission ≤9. RESULTS: The remission rate after 12 months was higher in the group where ozone concentration was below or equal to the median for the study population (P <0.001). Moreover, the patients in the group where ozone levels were above the median, presented lower C­peptide levels (P = 0.01), higher HbA1c concentration (P = 0.005), and higher daily insulin requirements (P = 0.02) after 12 months from the diagnosis. Also, in the group of participants achieving remission, the ambient ozone level was lower (P <0.001). In a multivariable logistic regression analysis, the increased ozone concentration in the month of diagnosis was the variable that influenced the lack of remission after 12 months, independently of sex and smoking (P <0.001). CONCLUSIONS: Increased ozone level may exacerbate metabolic outcomes and reduce remission in T1D.

Methods of Assessment of Physical Capacity in People with Diabetes Mellitus Type 1.

BACKGROUND: The article aims to present the most popular methods of assessing physical capacity. Moreover, the article sheds light on the beneficial impact of improving physical capacity in people with Diabetes Mellitus type 1 (DM1). METHODS: A computer-based literature search of PubMed, SCOPUS and Web of Science included studies up to September 2022. RESULTS: The significant role of regular physical exertion could be observed in the group of people suffering from DM1, which implicates a positive correlation between the activity and the remission time. A suitable and objective indicator of sport influence on the organism is physical capacity (PC), which describes the efficiency of the cardiovascular system and its correlation between BMI, sex, and age. PC is mostly shown as VO2max. Well metabolically controlled DM1 is not a contraindication to stress test. Even though physical activity is closely related to human history, the range of research into the importance of PC is still limited to particular groups of patients, which presents an opportunity for further research and future conclusions. CONCLUSIONS: Undertaking physical activities has a multidirectional influence on the organism. According to up-to-date knowledge, various methods of PC assessment are available. Patients can choose more easily accessible, simpler, and cheaper options like CRT, RT, and HST which do not need specialized equipment and skills. They can also decide on more advanced examinations like ergospirometry, where direct measurements of VO2max and other cardiorespiratory parameters are made.

Patient-perceived benefits and risks of off-label use of SGLT2 inhibitors and GLP-1 receptor agonists in type 1 diabetes: a structured qualitative assessment.

Background: Patients with type 1 diabetes mellitus (T1DM) may have suboptimal glucose control and are interested in the use of adjuvant therapies. Objectives: To determine, from the patients' perspective, the reasons for initiation of glucagon-like peptide 1 receptor agonist (GLP-1RA) and/or sodium glucose cotransporter 2 inhibitor (SGLT2i) in treating T1DM; perceived benefits/side effects, reasons for discontinuation, and willingness to reinitiate therapy. Design: Retrospective chart review with structured telephone interviews. Methods: We identified patients with T1DM treated with a GLP-1RA and/or SGLT2i for >3 months at University of Texas Southwestern Medical Center (Dallas, TX, USA) and Poznan University (Poznan, Poland). We conducted structured telephone interviews regarding their experiences. Results: We interviewed 68 participants treated with GLP-1RA and 82 with SGLT2i. Treatment was initiated for improving glycemic control (as reported by 61.8% versus 81.7% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (51.4% versus 23.2%) and to reduce insulin requirement (13.2% versus 11%). Most participants (86.8% of GLP-1RA and 89.0% of SGLT2i users) reported ⩾1 benefit attributed to therapy. Reported benefits were improved glycemic control (reported by 58.8% versus 82.9% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (63.2% versus 30.5%), and reduced insulin requirement (27.9% versus 34.1%). More GLP-1RA users reported side effects versus SGLT2i users (63.2% versus 36.6%); 22.6% discontinued GLP-1RA due to side effects versus 11.0% SGLT2i users. Diabetic ketoacidosis (DKA) was reported by 4.9% of SGLT2i users, but none in GLP-1RA users. Of those who discontinued medication, 60.7% of GLP-1RA versus 56.0% of SGLT2i prior users were willing to reinitiate treatment. Conclusions: Patients with T1DM report initiating adjuvant treatment with GLP-1RA and/or SGLT2i to improve glycemic control and lose weight; most patients reported perceived benefits from these therapies. Side effects (including DKA) are reported more commonly in real life than in clinical trials. Given patient interest in these medications, further studies should evaluate the long-term risk-benefits ratio in larger cohorts.

Physical Activity Protects Women with Type 1 Diabetes from Sexual Dysfunctions.

The aim of the study was to evaluate the relationship between physical activity and sexual function in women with type 1 diabetes mellitus (T1DM). The study group consisted of 171 women with T1DM. All the participants voluntarily filled out anonymous questionnaires. Women who were sexually inactive or had some psychological, psychiatric, or endocrine diseases were excluded from the analysis. The scores about sexual function were obtained using a Female Sexual Function Index (FSFI) questionnaire. Results equal to or below 26 points indicate clinically significant sexual dysfunction. Physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Participants were divided into two groups depending on the Metabolic Equivalent of Task (MET-min/week) score with a cutoff point 3000 MET-min/week. Results above 3000 points indicate higher physical activity in woman. There were statistically significant differences in lubrication, orgasm, pain, satisfaction, and total score of FSFI. A positive correlation was revealed between results in total FSFI score and MET-min/week score (Rs = 0.18, p = 0.016). Univariate logistic regression does not show significant associations, but the multivariate logistic regression model shows an association between the MET-min/week and the total FSFI score. The higher the MET-min/week score, the higher the FSI score, and thus better sexual function.

Arterial stiffness and the non-dipping pattern in type 1 diabetes males with and without erectile dysfunction.

Arterial stiffness (AS) and non-dipping pattern are early predictors of cardiovascular diseases but are not used in clinical practice. We aimed to assess if AS and the non-dipping pattern are more prevalent in the erectile dysfunction (ED) group than in the non-ED group among subjects with type 1 diabetes (T1DM). The study group consisted of adults with T1DM. Aortic pulse wave velocity (PWV Ao)-a marker of increased AS, central systolic blood pressure, and heart rate (HR) were measured with a brachial oscillometric device (Arteriograph 24). Erectile dysfunction (ED) was assessed by the International Index of Erectile Function-5. A comparison between the groups with and without ED was performed. Of 34 investigated men with T1DM, 12 (35.3%) suffered from ED. The group with ED had higher mean 24 h HR (77.7 [73.7-86.5] vs 69.9 [64.0-76.8]/min; p = 0.04, nighttime PWV Ao (8.1 [6.8-8.5] vs 6.8 [6.1-7.5] m/s; p = 0.015) and prevalence of non-dipping SBP Ao pattern (11 [91.7] vs 12 [54.5]%; p = 0.027) than individuals without ED. The presence of ED detected a central non-dipping pattern with a sensitivity of 47.8% and a specificity of 90.9%. The central non-dipping pattern was more prevalent and the nighttime PWV was higher in T1DM subjects with ED than in those without ED.

Molecular Changes in Cells of Patients with Type 2 Diabetes Mellitus Depending on Changes in Glycemia Level in the Context of Lifestyle-An Overview of the Latest Scientific Discoveries.

Diabetes mellitus is a significant health problem for medicine and economics. In 80-90% of cases, it is type 2 diabetes (T2DM). An essential aspect for people with T2DM is to control blood glucose levels and avoid significant deviations. Modifiable and non-modifiable factors influence the incidence of hyperglycemia and, sometimes, hypoglycemia. The lifestyle modifiable factors are body mass, smoking, physical activity, and diet. These affect the level of glycemia and impact molecular changes. Molecular changes affect the cell's primary function, and understanding them will improve our understanding of T2DM. These changes may become a therapeutic target for future therapy of type 2 diabetes, contributing to increasing the effectiveness of treatment. In addition, the influence of external factors (e.g., activity, diet) on each domain of molecular characterization has gained importance towards a better understanding of their role in prevention. In the current review, we aimed to collect scientific reports on the latest research about modifiable factors connected with the style of life which affect the glycemic level in the context of molecular discoveries.

Indirect insulin resistance markers are associated with nonalcoholic fatty liver disease in type 1 diabetes.

INTRODUCTION: Insulin resistance (IR) in type 1 diabetes mellitus (T1DM) is associated with increased insulin dose requirements, poor glycemic control, and elevated risk of chronic complications. IR increases lipid synthesis and hepatic lipid content. Disruption in hepatic lipid accumulation and export leads to liver steatosis resulting in nonalcoholic liver disease (NAFLD). OBJECTIVES: The aim of the study was to explore the relationship between indirect IR markers and NAFLD in T1DM. PATIENTS AND METHODS: We analyzed 151 patients with T1DM (59 men, 92 women), with a median (interquartile range [IQR]) age of 40 (33-47) years and a median (IQR) diabetes duration of 19 (13-21)years. The median (IQR) value of glycated hemoglobin (HbA1c) was 7.5% (6.8%-8.%; 58 [51-66] mmol/mol). The following indirect IR markers were evaluated: estimated glucose distribution rate (eGDR), visceral adiposity index (VAI), and the triglyceride to high­density lipoprotein cholesterol ratio (TG/HDL­C). Fatty infiltration of the liver was quantified using transient elastography. Presence of NAFLD was defined as a controlled attenuation parameter value of 238 dB/m or greater. RESULTS: NAFLD was observed in 65 patients (43%). The participants with NAFLD were less insulin­sensitive (eGDR, 8.93 [6.39-9.97] vs 9.94 [8.09-11.13] mg/kg/min; P = 0.001; VAI, 1.52 [1.2-2.64] vs 1.34 [0.92-1.74]; P = 0.014; TG/HDL­C ratio, 1.35 [0.95-2.11] vs 1.11 [0.77-1.6]; P = 0.02) and were characterized by higher HbA1c values (7.75% [7.2%-8.4%] vs 7.3% [6.5%-8.1%]; 61 [55-68] vs 56 [48-65] mmol/mol; P = 0.02) than the patients without the disease. In a multivariable regression analysis adjusted for sex, diabetes duration, and HbA1c level, indirect IR markers were independently associated with NAFLD (eGDR: odds ratio [OR], 0.86; 95% CI, 0.77-0.97; P = 0.01; VAI: OR, 1.61; 95% CI, 1.05-2.49; P = 0.03, TG/HDL­C ratio: OR, 1.88; 95% CI, 1.11-3.18; P = 0.02). CONCLUSIONS: In T1DM, NAFLD is more likely to be found in individuals with lower insulin sensitivity.

Independent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes.

BACKGROUND AND AIM: Low insulin sensitivity (IS) increases Type 1 diabetes (T1D) complication risk and can be estimated by simple formulae developed from complex euglycemic hyperinsulinaemic clamp studies. We aimed to validate these formulae using independent clamp data. METHODS: Clamps were performed in 104 T1D adults. Measured glucose disposal rate (GDR) was correlated with eGDR and eLog10 M/I calculated by five IS formulae. RESULTS: Correlations ranged between 0.23-0.40. Two IS formulae (by the authors), using age, sex, HDL-C, HbA1c, pulse pressure, BMI, and waist-hip-ratio had the highest correlation with measured GDR and the best performance in detecting low IS.

An extremely obese young man with newly diagnosed diabetes - classification dilemmas.

Not required for Clinical Vignettes.

Higher NADH Dehydrogenase [Ubiquinone] Iron-Sulfur Protein 8 (NDUFS8) Serum Levels Correlate with Better Insulin Sensitivity in Type 1 Diabetes.

OBJECTIVE: The aim of the study was to evaluate NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 (NDUFS8) serum concentration as a marker of Complex I, and the relationship with insulin resistance in type 1 diabetes mellitus (T1DM). DESIGN AND METHODS: Participants were adults with T1DM, recruited over the course of 1 year (2018-2019). NDUFS8 protein serum concentration was measured using the ELISA test. Insulin resistance was evaluated with indirect marker estimated glucose disposal rate (eGDR). The group was divided on the base of median value of eGDR (higher eGDR-better insulin sensitivity). RESULTS: The study group consists of 12 women and 24 men. Medians of eGDR and NDUFS8 protein concentration are 7.6 (5.58-8.99) mg/kg/min and 2.25 (0.72-3.81) ng/mL, respectively. The group with higher insulin sensitivity has higher NDUFS8 protein serum concentration, lower waist to hip ratio (WHR), body mass index (BMI), and they are younger. A negative correlation is observed between NDUFS8 protein serum concentration and WHR (rs = -0.35, p = 0.03), whereas a positive correlation is observed between NDUFS8 protein serum concentration and eGDR (rs = 0.43, p = 0.008). Univariate logistic regression shows a significant association between insulin sensitivity and lower age, as well as a higher NDUFS8 serum level. A multivariate logistic regression model confirms the significance (AOR 2.38 (1.04-5.48). p = 0.042). Multivariate linear regression confirms a significant association between insulin sensitivity and better mitochondrial function (beta = 0.54, p = 0.003), independent of age, duration of diabetes, and smoking. CONCLUSIONS: Higher NDUFS8 protein serum concentration is associated with higher insulin sensitivity among adults with T1DM.

Erectile Dysfunction in Individuals with Type 1 Diabetes is Associated with Long-term Metabolic Control and Diabetic Complications: A Cross-Sectional Study.

Background Erectile dysfunction (ED) affects approximately 38% of individuals with type 1 diabetes (T1DM). Skin autofluorescence (AF) reflects skin advanced glycation end product (AGE) deposits and is a marker of long-term glycemia control. Objective The study investigates the relationship between ED and diabetes control in patients with T1DM. Methods Adult patients with T1DM visiting the Diabetology Department were cross-sectionally investigated. Medical history, anthropometric features, and laboratory findings were collected. All individuals filled the International Index of Erectile Function (IIEF-5). IIEF-5 total score < 22 represented the presence of ED. AF was measured on the volar aspect of the forearm using AGE Reader. Insulin resistance (IR) was assessed by the estimated glucose disposal rate. Descriptive statistics and multivariate logistic regression analyses were performed. The adjusted covariates were general risk factors of ED. Results Of a total of n = 70 patients, n = 30 (42.9%) suffered from ED. The presence of ED was associated with higher glycated hemoglobin level (OR, 95% CI; 1.62, 1.02-2.60; p = 0.043), presence of at least one diabetic complication (3.49, 1.10-11.03; p = 0.03), and skin AF (9.20, 1.60-52.94; p = 0.01), but not with IR (0.78, 0.57-2.60; p = 0.12). Skin AF values ≥ 2.2 indicates presence of ED with a sensitivity of 70.0% and a specificity of 77.5%. Area under the curve was equal to 0.72 (95% CI: 0.60-0.85). Conclusions The presence of ED in individuals with T1DM is associated with HbA1c, the presence of at least one diabetic complication, and skin AF.

Arterial Stiffness and Type 1 Diabetes: The Current State of Knowledge.

The most common cause of mortality among people with type 1 diabetes is cardiovascular diseases. Arterial stiffness allows predicting cardiovascular complications, cardiovascular mortality, and all-cause mortality. There are different ways to measure arterial stiffness; the gold standard is pulse wave velocity. Arterial stiffness is increased in people with type 1 diabetes compared to healthy controls. It increases with age and duration of type 1 diabetes. Arterial stiffness among people with type 1 diabetes positively correlates with systolic blood pressure, obesity, glycated hemoglobin, waist circumference, and waist to hip ratio. It has a negative correlation with the estimated glomerular filtration rate, high-density lipoprotein, and the absence of carotid plaques. The increased arterial stiffness could result from insulin resistance, collagen increase due to inadequate enzymatic glycation, and endothelial and autonomic dysfunction. The insulin-induced decrease in arterial stiffness is impaired in type 1 diabetes. There are not enough proofs to use pharmacotherapy in the prevention of arterial stiffness, but some of the medicaments got promising results in single studies, for example, renin-angiotensin-aldosterone system inhibitors, statins, and SGLT2 inhibitors. The main strategy of prevention of arterial stiffness progression remains glycemic control and a healthy lifestyle.

Is it time to change the goals of lipid management in type 1 diabetes mellitus? Changes in apolipoprotein levels during the first year of type 1 diabetes mellitus. Prospective InLipoDiab1 study.

Introduction: Apolipoprotein complement is a critical determinant of lipoprotein function and metabolism. The relation between exogenous insulin and apolipoproteins (apos) in newly diagnosed type 1 diabetes mellitus (T1DM) has not yet been studied extensively. The aim of this study was to prospectively observe the changes in serum apos AI (apo AI) and AII (apo AII) in patients with newly diagnosed T1DM and their association with the daily insulin requirement. Material and methods: Thirty-four participants of the InLipoDiab1 study aged 26 (IQR: 22-32) were enrolled in this analysis. Apolipoprotein AI and AII concentrations were assessed at diagnosis and at follow-up after 3 weeks, 6 months, and 1 year of insulin treatment. The daily dose of insulin (DDI) was calculated as the amount of short- and long-acting insulin at discharge from the hospital and at follow-up visits. Results: The changes in apo AI concentration were observed after 3 weeks of insulin treatment (p = 0.04), with the largest increase between 3 weeks and 6 months of observation (p < 0.001). Apolipoprotein AII level did not change significantly after 3 weeks, while a significant increase was observed between 3 weeks and 6 months of treatment (p < 0.001). The correlations between DDI and apo concentration were not statistically significant. Conclusions: In the first year of T1DM, there is a significant increase in apos concentration. Due to the significant deviation of apos concentration from accepted norms, changes in the recommendations of lipid control criteria in T1DM may be considered.

The Other Face of Insulin-Overdose and Its Effects.

Insulin is the most effective glycemic-lowering drug, and for people suffering from type 1 diabetes it is a life-saving drug. Its self-dosing by patients may be associated with a higher risk of overdose, both accidental and deliberate. Insulin-induced hypoglycemia causes up to 100,000 emergency department calls per year. Cases of suicide attempts using insulin have been described in the literature since its introduction into therapy, and one of the important factors in their occurrence is the very fact of chronic disease. Up to 90% of patients who go to toxicology wards overdose insulin consciously. Patients with diabetes are burdened with a 2-3 times higher risk of developing depression compared to the general population. For this reason, it is necessary to develop an effective system for detecting a predisposition to overdose, including the assessment of the first symptoms of depression in patients with diabetes. A key role is played by a risk-conscious therapeutic team, as well as education. Further post-mortem testing is also needed for material collection and storage, as well as standardization of analytical methods and interpretation of results, which would allow for more effective detection and analysis of intentional overdose-both by the patient and for criminal purposes.