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.

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.

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.

Association between physical activity before diagnosis and the presence of clinical remission in type 1 diabetes - InlipoDiab1 study.

AIM: To investigate whether physical activity is associated with the occurrence of remission in adults with type 1 diabetes. METHODS: Ninety nine adult participants with newly diagnosed type 1 diabetes were enroled into a prospective, observational study. The participants were advised to exercise 2-3 times a week with moderate intensity for a one-year period. Physical activity was assessed by a self-administrated questionnaire on every fourth visit. We counted the months in which participants fulfiled a partial-remission criteria: HbA1c < 6.5%, C-peptide > 0.5 ng/ml, and daily dose of insulin <0.3 U/kg/day. We assigned the participants to two groups: MORE EFFORT and LESS EFFORT, depending on the median value of physical activity in the studied population. RESULTS: The occurrence of the remission achieved statistical significance at 6th month with a greater prevalence in MORE EFFORT group (55% vs. 35% p = 0.047). In multivariate logistic regression analysis for the occurrence of remission at 12th month, physical activity before the diagnosis was the only variable that influences the occurrence of the remission (adjusted odds ratios = 3.32 [95% confidence intervals 1.25-8.80]; p = 0.02). CONCLUSION: In adults with newly diagnosed type 1 diabetes physical activity before the diagnosis is associated with higher occurrence of remission.

Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study.

BACKGROUND AND AIMS: Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM. METHODS AND RESULTS: 57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA. A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP. CONCLUSION: Exogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.

Can We Prevent Mitochondrial Dysfunction and Diabetic Cardiomyopathy in Type 1 Diabetes Mellitus? Pathophysiology and Treatment Options.

Type 1 diabetes mellitus is a disease involving changes to energy metabolism. Chronic hyperglycemia is a major cause of diabetes complications. Hyperglycemia induces mechanisms that generate the excessive production of reactive oxygen species, leading to the development of oxidative stress. Studies with animal models have indicated the involvement of mitochondrial dysfunction in the pathogenesis of diabetic cardiomyopathy. In the current review, we aimed to collect scientific reports linking disorders in mitochondrial functioning with the development of diabetic cardiomyopathy in type 1 diabetes mellitus. We also aimed to present therapeutic approaches counteracting the development of mitochondrial dysfunction and diabetic cardiomyopathy in type 1 diabetes mellitus.

Brain-Derived Neurotrophic Factor and Diabetes.

Diabetes and its chronic complications still represent a great clinical problem, despite improvements made in the diagnosis and treatment of the disease. People with diabetes have a much higher risk of impaired brain function and psychiatric disorders. Neurotrophins are factors that protect neuronal tissue and improve the function of the central nervous system, and among them is brain-derived neurotrophic factor (BDNF). The level and function of BDNF in diabetes seems to be disturbed by and connected with the presence of insulin resistance. On the other hand, there is evidence for the highly beneficial impact of physical activity on brain function and BDNF level. However, it is not clear if this protective phenomenon works in the presence of diabetes. In this review, we summarize the current available research on this topic and find that the results of published studies are ambiguous.

Sexual Dysfunction Is a More Common Problem in Young Women with Type 1 Diabetes than in Healthy Women.

The aim of the study was to analyze the relationship between the presence of type 1 diabetes and sexual dysfunction among young women. The study group consisted of 230 women, including 70 healthy and 160 with diabetes mellitus type 1 (DM1). All the participants voluntarily filled anonymous questionnaire. The results regarding sexual function were obtained using a Female Sexual Function Index (FSFI) questionnaire. Statistical analysis was performed for sexually active people. In the study group, 180 women declared sexual activity: 62 healthy (88%) and 118 with DM1 (82.5%). Women with DM1 in comparison with healthy women were older, had higher BMI, weight, and had more pack-years of cigarette smoking. Women with DM1 had lower results in FSFI and more often achieved scores below the clinical cutoff point. In a multiple linear regression model, the presence of diabetes predicted lower FSFI results. DM1 is independently associated with the presence of impaired sexual function. Sexual dysfunctions are more common among young women with DM1 than in healthy controls. The relationship is significant despite of the age, duration of diabetes, body weight, and presence of angiopathy.

Visceral adiposity index as a useful tool for the assessment of cardiometabolic disease risk in women aged 65 to 74.

BACKGROUND: The visceral adiposity index (VAI) is considered to be a reliable indicator of adipose tissue dysfunction and cardiometabolic disease risk. The aim of this study was to evaluate its usefulness in assessing cardiometabolic risk in a sample of elderly women living in a rural-urban community in central Poland. METHODS: A total of 365 women aged 65 to 74 years were included in this cross-sectional study. All patients were interviewed to obtain their history of diabetes mellitus, myocardial infarction, stroke, and revascularization. For all participants, anthropometric measurements were performed, then body mass index (BMI) and waist/hip ratio were calculated. Blood pressure was measured on the arm and on both ankles, and the ankle/brachial index was calculated. Blood samples were collected for the assessment of glycemia, lipid profile, and creatinine level. In patients with elevated fasting glucose, the test was repeated, or an oral glucose tolerance test was performed where appropriate. Finally, carotid intima-media thickness was measured in all women. RESULTS: The VAI of participants was significantly correlated with a history of myocardial infarction, higher carotid intima-media thickness, diabetes, prediabetes, and impaired kidney function. Furthermore, VAI demonstrated a better correlation with these endpoints than BMI or waist circumference. CONCLUSIONS: The VAI can be considered a useful tool for the assessment of cardiometabolic disease risk in elderly women, with a score of ≥2.71 representing the cut-off point for identifying females at high risk. In such patients, screening for cardiovascular disease, abnormal glucose metabolism, and impaired kidney function should be routine practice.

Skin autofluorescence is associated with carotid intima-media thickness, diabetic microangiopathy, and long-lasting metabolic control in type 1 diabetic patients. Results from Poznan Prospective Study.

AIMS: Our aim was to assess the association between skin autofluorescence (AF) related to advanced glycation end products (AGEs) accumulation and long-term metabolic control, microvascular complications and carotid intima-media thickness (IMT) in an observational cohort of type 1 diabetes (DM1). METHODS: The analysis included 77 patients with DM1 (28 women and 49 men) aged 38 (IQR: 34-41), diabetes duration 15 (14-17), participating in Poznan Prospective Study (PoProStu). Skin AF was measured with AGE Reader (DiagnOptics). RESULTS: We found 50% of any microvascular complication; 37% of retinopathy, 37% of diabetic kidney disease and 22% of distal symmetrical neuropathy. Median carotid IMT was 0.57 (0.52-0.67) mm and skin AF 2.2 (IQR: 1.9-2.6). We found positive correlation between skin AF and patients' age (r=0.31, p=0.006), mean HbA1c from the observation time (r=0.35, p=0.001) and IMT (r=0.39, p<0.001). In multivariate logistic regression presence of microvascular complications was independently associated with skin AF: for retinopathy (OR 3.49; 95% CI: 1.08-11.28, p=0.03), for diabetic kidney disease (OR 3.62; 95% CI: 1.16-11.28, p=0.02), for neuropathy (OR 5.01; 95% CI: 1.21-20.77, p=0.02) and for any microangiopathy (OR 3.13; 95% CI: 1.06-9.18, p=0.03). CONCLUSION: Skin AF is a reliable marker of past glycemic control of diabetes. Increased accumulation of AGEs is related to the presence of diabetic microangiopathy as well as subclinical macroangiopathy in patients with type 1.

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.

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.

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.

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.

An online tool using clinical factors to estimate the probability of partial clinical remission of adult-onset Type 1 diabetes.

A type 1 diabetes (T1D) diagnosis is often followed by a period of reduced exogenous insulin requirement, with acceptable glucose control, called partial clinical remission (pCR). Various criteria exist to define pCR, which is associated with better clinical outcomes. We aimed to develop formulae and a related online calculator to predict the probability of pCR at 3- and 12-months post-T1D diagnosis. We analysed data from 133 adults at their T1D diagnosis (mean ± SD age: 27 ± 6 yrs., HbA1c 11.1 ± 2.0 %, 98 ± 22 mmol/mol), 3- and 12-months later. All patients were enrolled in the prospective observational InLipoDiab1 study (NCT02306005). We compared four definitions of pCR: 1) stimulated C-peptide >300 pmol/l; 2) insulin dose-adjusted HbA1c ≤9 %; 3) insulin dose <0.3 IU/kg/24 h; and HbA1c ≤6.4 % (46 mmol/mol); and 4) insulin dose <0.5 IU/kg/24 h and HbA1c <7 % (53 mmol/mol). Using readily available demographics and clinical chemistry data exhaustive search methodology was used to model pCR probability. There was low concordance between pCR definitions (kappa 0.10). The combination of age, HbA1c, diastolic blood pressure, triglycerides and smoking at T1D onset predicted pCR at 12-months with an area under the curve (AUC) = 0.87. HbA1c, triglycerides and insulin dose 3-mths post-diagnosis had an AUC = 0.89. A related calculator for pCR in adult-onset T1D is available at http://www.bit.ly/T1D-partial-remission.

The association of thyroid autoimmunity with ovarian reserve in women with type 1 diabetes with and without polycystic ovary syndrome.

The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m2) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (ß = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.

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.

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.

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.

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.