T2D Patients Research Articles

Comparison of SGLT1, SGLT2, and Dual Inhibitor biological activity in treating Type 2 Diabetes Mellitus.

Diabetes Mellitus Type 2 (T2D) is an emerging health burden in the USand worldwide, impacting approximately 15% of Americans. Current front-line therapeutics for T2D patients include sulfonylureas that act to reduce A1C and/or fasting blood glucose levels, or Metformin that antagonizes the action of glucagon to reduce hepatic glucose production. Next generation glucomodulatory therapeutics target members of the high-affinity glucose transporter Sodium-Glucose-Linked-Transporter (SGLT) family. SGLT1 is primarily expressed in intestinal epithelium, whose inhibition reduces dietary glucose uptake, whilst SGLT2 is highly expressed in kidney - regulating glucose reabsorption. A number of SGLT2 inhibitors are FDA approved whilst SGLT1 and dual SGLT1 & 2 inhibitor are currently in clinical trials. Here, we discuss and compare SGLT2, SGLT1, and dual inhibitors' biochemical mechanism and physiological effects.

M-index as a predictor of glycemia normalization in T2D patients early after bariatric surgery

There are several models for predicting remission of type 2 diabetes mellitus (T2D) a year after bariatric surgery — DiaRem, ABSD, IMS, etc. However, these models cannot be used to predict the early normalization of glycemia (within a few months after surgery). These models also do not include the assessment of insulin resistance (IR).AIM. To assess the effect of insulin resistance on the development of remission of T2D after bariatric surgery.METHODS: The study included 42 patients with T2D and severe obesity, who underwent bariatric surgery. Baseline assessment included hyperinsulinemic euglycemic clamp test (with the determination of the M-index (mg/kg/min), and evaluation of HOMA-IR index. Glycemia normalization was determined by self-monitoring (<6.1 mmol/l at fasting state and <7.8 mmol/l 2 hours after meals) as well as by HbA1c (<6.5%, starting 3 months after surgery). We used ROC analysis to determine the possibility of using IR indicators in predicting of the normalization of glycemia after bariatric surgery. The cut off value was determined using the Yuden criterion.RESULTS: All patients were severely insulin resistant. The median M-index before surgery was 1.535 mg/kg/min, the HO-MA-IR index was 10.0. During 1 year after surgery the increasing number of patients reached normal glycemia: 7 (16.7%) patients in 1 month, 22 (52.4%) patients after 3 months, 31 (73.8%) patients after 6 months, 35 (83.3%) patients after 12 months. In ROC analysis the optimal threshold the M-index was 1.876 mg/kg/min.CONCLUSION: The value of the M-index > 1.876 mg/kg/min can be used to predict the glycemia normalization early after bariatric surgery.

DNA methylation differences within INS, PTPN22 and IL2RA promoters in lymphocyte subsets in children with type 1 diabetes and controls

We elucidated the effect of four known T1D-susceptibility associated single nucleotide polymorphism (SNP) markers in three genes (rs12722495 and rs2104286 in IL2RA, rs689 in INS and rs2476601 in PTPN22) on CpG site methylation of their proximal promoters in different lymphocyte subsets using pyrosequencing. The study cohort comprised 25 children with newly diagnosed T1D and 25 matched healthy controls. The rs689 SNP was associated with methylation at four CpG sites in INS promoter: −234, −206, −102 and −69. At all four CpG sites, the susceptibility genotype AA was associated with a higher methylation level compared to the other genotypes. We also found an association between rs12722495 and methylation at CpG sites −373 and −356 in IL2RA promoter in B cells, where the risk genotype AA was associated with lower methylation level compared to the AG genotype. The other SNPs analyzed did not demonstrate significant associations with CpG site methylation in the examined genes. Additionally, we compared the methylation between children with T1D and controls, and found statistically significant methylation differences at CpG −135 in INS in CD8+ T cells (p = 0.034), where T1D patients had a slightly higher methylation compared to controls (87.3 ± 7.2 vs. 78.8 ± 8.9). At the other CpG sites analyzed, the methylation was similar. Our results not only confirm the association between INS methylation and rs689 discovered in earlier studies but also report this association in sorted immune cells. We also report an association between rs12722495 and IL2RA promoter methylation in B cells. These results suggest that at least part of the genetic effect of rs689 and rs12722495 on T1D pathogenesis may be conveyed by DNA methylation.

Level of IL-6 and IL-8 and their associations with non-alcoholic fatty liver disease in patients with type 2 diabetes

non-alcoholic fatty liver disease (NAFLD) is indicated by the accumulation of lipids within the hepatocytes exceeding 5% of liver weight without excessive alcohol intake and secondary liver diseases. The efforts of many scientists worldwide are focused on improving the understanding of pathogenic processes and triggers of NAFLD progression, with an emphasis on the simultaneous study of several pathophysiological pathways to identify disorders throughout the disease spectrum. The aim was to examine the serum levels of IL-6 and IL-8 and its associative relationships with anthropometric parameters and metabolic profiles in patients with T2D, depending on the presence of NAFLD. This cross-sectional study involved 375 patients aged 40–80 with type 2 diabetes. They were divided into 3 groups. The control group included 98 T2D patients without NAFLD. The main group included T2D patients with NAFLD, which was separated into two subgroups depending on the level of transaminases: normal (group 2A, n=150) and increased (group 2B, n=127) transaminases group. In order to identify predictors of rapid progression of liver fibrosis in patients with T2D, a sub-analysis was conducted, which included 82 patients from group 2. We found significant relationships between the level of studied interleukins and the components of the metabolic syndrome. Both IL-6 and Il-8 levels are significantly associated with gender, duration and severity of T2D, BMI, ALT, AST and total bilirubin level in a simple logistic regression analysis. However, step-by-step multiple logistic regression analysis revealed no reliable link between both cytokines and NAFLD development. From the other hand elevated IL-8 and decreased IL-6 had a significant effect on the fibrosis progression in patients with NAFLD associated with T2D. Our study has demonstrated significant links between the level of IL-6 and IL-8 and the components of the metabolic syndrome such as obesity or transaminase activity, but not with NAFLD itself.

Risk Factors for Nonalcoholic Fatty Liver Disease among Patients Referred to Radiological Departments at Hail Hospitals, KSA

Background: Nonalcoholic fatty liver disease (NAFLD) incidence and prevalence have increased globally. The gravity of this chronic disease comes from its ability to progress to cirrhosis and hepatocellular carcinoma, which are rising rapidly. Genetic, demographic, environmental, and clinical factors are significant in the occurrence of NAFL. This study aimed to assess risk factors that affect the occurrence of NAFLD. Methods and Results: This cross-sectional study was carried out at hospitals in the Hail Region, KSA. It included 160 patients: 76 were considered as control (normal liver), and 84 suffered from fatty liver (according to a US image). Sonography was carried out using a US scanner with curvilinear transducers having a frequency of 3.5MHz. The following data were obtained: age, BMI, clinical history, including long-term medication of more than 3 months (oral antidiabetic medications, hormone replacement therapy for hyperthyroidism, and antihypertensive drug), T2D, viral hepatitis, liver span, lipidemia, metabolic disorders, and weight loss. The prevalence of NAFLD increases significantly among patients taking medications for a long time and T2D patients (P<0.001). Hepatomegaly is one of the most common physical examination findings of NAFLD (P<0.001). Conclusion: A periodic US examination is helpful because it can reveal fatty infiltration of the liver in the early stages to avoid fatal complications, especially for patients with long-term medication or T2D. Other studies with larger sample sizes and different known risk factors are needed to discover all risk factors for the KSA population.

Positive Effects of Physical Activity on Prescription on Glycemic Control, Fitness, and Quality of Life in Newly Diagnosed Type 2 Diabetic Patients.

The aim was to investigate the effects of physical activity on prescription (PAP) compared with standard care (SC) in adult drug-naïve T2D patients. A randomized control trial was conducted with drug-naïve T2D patients attending an out-patient clinic Vietnam. Participants were randomly assigned to the PAP group (n+=+44) or the SC group (n+=+43). The PAP group received individualized recommendations for PA, intensive face-to-face training every two weeks. The SC group received the standard recommendations according to WHO guidelines. The mean HbA1c level change was larger (-10.6±6.4 mmol/mol) in the PAP group than in the SC group (-2.4±5.8 mmol/mol) (p<0.001). A one thousand step counts per day increase was significantly associated with a decrease of -2.43 mmol/mol in HbA1c [β=-2.43, 95%CI: (-2.94, -1.92]) in the PAP group. The fasting plasma glucose levels of the PAP group decreased significantly compared with the SC group. The VO2-max increased significantly more in the PAP group than in the SC group. PAP had clear positive effects on health-related Quality of Life [mean between group difference: 9.54 (95%CI 5.84,13.23)]. Insulin resistance, BMI, waist circumference, total cholesterol, LDL cholesterol and triglycerides were significantly more decreased in the PAP group than in the control group. In conclusion, the fact that even a small change in mean step counts over three months had a beneficial effect on health-related outcomes in drug-naïve T2D patients can have large implications for treatment and management practices, not least in a middle-income country like Vietnam.

Correlation Self-Compassion and Stress in Patients with Type II Diabetes Mellitus

Type 2 diabetes mellitus (T2D) in the elderly is an increasing health problem. Elderly patients with type 2 diabetes have a higher risk of diabetes complications and require appropriate treatment. This disease causes 4 million deaths annually, accounting for 9 percent of all deaths worldwide. The purpose of the study was to assess the correlation of self-compassion and stress on T2D patients at the Lubuk Buaya Health Center. This study used a cross- sectional study design. 85 elderly people with T2D referring to the Lubuk Buaya Health Center were enrolled through a simple randomized sampling method from November to February 2022. In order to collect data, the Depression Anxiety Stress Scales (DASS) and the self-compassion scale (SCS) were used. In addition, to analyze the data, pearson product moment test methods were done using SPSS V.22 software. The results show that there is a significant correlation between self-compassion and stress in patients T2D. Self-compassion is one of the most effective methods for reducing stress in diabetic patients. Consequently, therapists, counselors, and psychologists are encouraged to employ self-compassion training to reduce stress in T2D patients. Keywords: Diabetes Melitus, Type II, Stress, Self-Compassion

The Clinical Utility of Transcription Factor 7-Like-2 (TCF7L2) Gene Polymorphism rs12255372 in Type 2 Diabetes Mellitus

Abstract Background Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia resulting from defect of insulin secretion and/or increased cellular resistance to insulin. Aim of the Work Our study aimed to evaluate the association of TCF7L2 rs12255372 gene polymorphism with T2D. Patients and Methods The study was conducted on forty seven (47) diabetic patients who were recruited from the out-patient clinic and in-patient Department of Endocrinology at Ain Shams University Hospitals; in addition, twenty three (23) age- and sex-matched healthy subjects taken as healthy control group. Assay of TCF7L2 rs12255372 gene polymorphism was performed by real-time PCR analysis. Results The study had demonstrated that there was no significant association between TCF7L2 rs12255372 G&amp;gt;T gene polymorphism and T2D. However, there was significant association between the concordance of risk T allele and the occurrence of dyslipidemia. Conclusion Our study did not confirm the presence of significant association between the TCF7L2 rs12255372 (G/T) polymorphism and T2D inspite of higher frequency of T allele in diabetic patients than healthy controls, however, it pointed to the association between the concordance of T allele in T2D patients with poor glycemic control with sulphonylurea.

Clinical outcomes of a digitally supported approach for self-management of type 2 diabetes mellitus.

Self-management of Type 2 diabetes mellitus (T2D) is challenging. Regular self-monitoring of blood glucose and healthy lifestyles are required to improve glycometabolic control, thus delaying diabetes complications, and reducing hospitalizations. Digital technologies can empower patients in their disease management promoting self-management and motivation to change behaviors. We report the results of an exploratory trial aimed at evaluating the metabolic outcomes of using digital solutions for T2D self-management developed in the ProEmpower project, a European Commission funded Pre-Commercial Procurement. Two digital solutions, DM4All and DiaWatch, which were codesigned with providers, patients, and caregivers, enabled the collection of clinical parameters by the patient using a smartphone integrated with the medical devices (glucometer, sphygmomanometer, scale, smart watch for heart rate monitoring and step counter). Data were automatically sent to the shared care plan allowing professionals to monitor adherence to treatment, set goals, and communicate more effectively with patients. At baseline and after an average follow-up of 8 months, glycosylated hemoglobin (HbA1c), body weight, blood pressure, and blood lipids were measured in 100 T2D patients using the ProEmpower solutions across different diabetes centers in Campania Region, age 45-79 years, both genders, and compared with a Control cohort of T2D patients (n = 100) with similar clinical characteristics and followed for a comparable period of observation in the same centers. At baseline, the ProEmpower participants and the Control subjects were on average overweight, with a similar BMI in the two cohorts, and mean HbA1c was at acceptable levels (around 7.0%). After the 8 month exploratory trial, body weight, HbA1c, systolic and diastolic blood pressure, and plasma and LDL-cholesterol significantly decreased in the ProEmpower participants compared to baseline (p < 0.05 for all). The changes in systolic and diastolic blood pressure, and plasma and LDL-cholesterol were significantly different from those observed in the Control cohort (p < 0.05 for all). This pilot study showed positive effects on metabolic outcomes relevant to cardiovascular risk in T2D of adopting digital telemedicine self-monitoring solutions based on automation of measurements and coaching on healthy lifestyles promotion.

Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes

ObjectiveType 2 diabetes (T2D) is linked to metabolic, mitochondrial and inflammatory alterations, atherosclerosis development and cardiovascular diseases (CVDs). The aim was to investigate the potential therapeutic benefits of GLP-1 receptor agonists (GLP-1 RA) on oxidative stress, mitochondrial respiration, leukocyte-endothelial interactions, inflammation and carotid intima–media thickness (CIMT) in T2D patients. Research design and methodsType 2 diabetic patients (255) and control subjects (175) were recruited, paired by age and sex, and separated into two groups: without GLP-1 RA treatment (196) and treated with GLP-1 RA (59). Peripheral blood polymorphonuclear leukocytes (PMNs) were isolated to measure reactive oxygen species (ROS) production by flow cytometry and oxygen consumption with a Clark electrode. PMNs were also used to assess leukocyte-endothelial interactions. Circulating levels of adhesion molecules and inflammatory markers were quantified by Luminex's technology, and CIMT was measured as surrogate marker of atherosclerosis. ResultsTreatment with GLP-1 RA reduced ROS production and recovered mitochondrial membrane potential, oxygen consumption and MPO levels. The velocity of leukocytes rolling over endothelial cells increased in PMNs from GLP-1 RA-treated patients, whereas rolling and adhesion were diminished. ICAM-1, VCAM-1, IL-6, TNFα and IL-12 protein levels also decreased in the GLP-1 RA-treated group, while IL-10 increased. CIMT was lower in GLP-1 RA-treated T2D patients than in T2D patients without GLP-1 RA treatment. ConclusionsGLP-1 RA treatment improves the redox state and mitochondrial respiration, and reduces leukocyte-endothelial interactions, inflammation and CIMT in T2D patients, thereby potentially diminishing the risk of atherosclerosis and CVDs.

Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes

Introduction/aimsDiabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.MethodsA total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (Ktrans), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).ResultsThe Ktrans (HC 0.031 min−1 ± 0.009, T2D 0.043 min−1 ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z‑scores of thermal and mechanical detection correlated with Ktrans (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z‑scores of thermal pain and Vp (r = −0.57; p = 0.015) correlated negatively.DiscussionThe findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.

Identification of Sociodemographic and Clinical Factors Influencing the Feeling of Stigmatization in People with Type 1 Diabetes.

A large percentage of people with type 1 diabetes experience stigma, which may directly affect diabetes management. Moreover, it may adversely influence the acceptance of the disease and, thus, the treatment process, including compliance with medical and dietary recommendations. Therefore, it is important to seek adequate forms of counteracting the phenomenon of stigmatization. Thus, the aim of the study was to determine the factors influencing the level of perceived stigma by T1D patients, with particular emphasis on sociodemographic factors (including sex, place of residence, and education) and clinical factors related to the course of the disease. An observational cross-sectional online questionnaire was conducted in a group of 339 people with T1D. The link to the questionnaire was shared via social media. The DSAS-1 questionnaire translated into Polish was used as the research tool. A moderate level of stigmatization was found (49.78 ± 14.54 points). It was significantly lower in people living in small towns compared to rural residents (ß = -0.121, p = 0.038), lower in people in relationships compared to those who are single (ß = -0.175, p = 0.001), in people diagnosed with T1D at an older age (ß = -0.107, p = 0.048), and in those who rated their financial situation as very good vs. bad (ß = -0.314, p < 0.001). It was also found that the level of stigma significantly decreased with age (ß = -0.181, p = 0.001). In addition, a significantly higher stigma perception was uncovered in the group of people with HbA1C > 7% than in the group ≤ 7% (ß = 0.118, p = 0.030). Due to the occurrence of stigma among people with T1D, which can directly affect the management of diabetes, effective and comprehensive efforts should be made to provide support to people with diabetes. It is also necessary to raise awareness among the general public and disseminate knowledge about diabetes, which can reduce stigmatization as a result. Anti-stigma messages should be included in the prevention programs about the potential side effects and risks associated with mistreating people with T1D.

Right Ventricular Dysfunction and Exercise Impairment in Patients with Heart Failure, Insulin Resistance, and Diabetes Mellitus: Insights from the T.O.S.CA. Registry (Cardiovascular Diabetology 2022).

Insulin resistance (IR) and type 2 diabetes mellitus (T2D) are known to affect the progression of chronic heart failure (CHF), but little evidence exists about the impact of IR and T2D on right ventricular dysfunction and exercise tolerance. Insights from the T.O.S.C.A. Registry: Echocardiographic hallmarks and cardiopulmonary exercise test (CPET) results were evaluated at baseline and after an average time of 36 months. T2D patients exhibited a greater intraventricular septum (IVS) thickness (11 ± 2 mm, 10 ± 2 mm, 10 ± 2 mm, in T2D, IR, and EU, respectively; p<.05) and LV wall thickness (0.34 ± 0.1, 0.32 ± 0.1, and 0.32 ± 0.1, in T2D, IR, and EU, respectively; p<.05). Moreover, T2D patients exhibited worse LV filling dynamics with larger left atrial volume index compared to IR and EU. Right ventricle dysfunction, expressed as a lower TAPSE/PASP ratio, was found in T2D [0.52(0.32-0.72)] than in EU and IR [0.60(0.30-0.90); p<.05]. T2D patients showed a significantly lower VO2 max peak when compared to IR and EU patients (15.8 ± 3.8 vs. 16.5 ± 4.3 vs. 18.4 ± 4.3 ml/Kg/min; p<.003), with an inverse relationship between the HOMAIR classes and VO2 max. Right ventricle structure and function deteriorated more rapidly in T2D, as suggested by more relevant deterioration in TAPSE/PASP ratio (-10% in EU patients, -14% in IR patients, -21% in T2D; p<.05). The study findings suggest that the right ventricle structure, function, and cardiopulmonary performance deteriorate with IR and, more evidently, due to chronic exposure to hyperglycemia in T2D. Impaired exercise tolerance, poor cardiorespiratory fitness, diastolic dysfunction, and left atrial enlargement predispose patients to poor quality of life, suboptimal adherence to physical activity, and an overall increase in the risk of all-cause and cardiovascular mortality. In addition, chronic hyperglycemia accelerates the progression of these alterations, especially in patients with poor glycemic control over time. Highly selective and even more non-selective sodium glucose transporter type 2 inhibitors and glucagon-like peptide 1 receptor agonists should be considered as the first-line therapy for improving CV outcomes in T2D and CHF. Further studies are needed to understand the role of these molecules in treating pre-clinical conditions, such as IR and metabolic syndrome.

The effects of acarbose treatment on cardiovascular risk factors in impaired glucose tolerance and diabetic patients: a systematic review and dose-response meta-analysis of randomized clinical trials.

Acarbose (ACB) seems to be an effective drug in the management of cardiovascular risk factors. However, no previous meta-analysis of randomized controlled trials (RCTs) has been done to evaluate the effects of ACB on cardiovascular risk factors on impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2D), and type 1 diabetes mellitus (T1D). We comprehensively searched electronic databases including Scopus, Web of Science, and PubMed for RCTs for related keywords up to September 2022. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI). The pooled analysis demonstrated that ACB treatment had a significant effect on fasting blood glucose (FBG) (WMD = -3.55 mg/dL; 95%CI: -6.29, -0.81; p = 0.011), fasting insulin (WMD = -6.73 pmoL/L; 95%CI: -10.37, -3.10; p < 0.001), HbA1c [WMD = -0.32%; 95%CI: -0.45, -0.20; p < 0.001], body weight (WMD = -1.25 kg; 95%CI: -1.79, -0.75; p < 0.001), body mass index (BMI) (WMD = -0.64 kg/m2; 95%CI: -0.92, -0.37; p < 0.001), tumor necrosis factor-alpha (TNF-α) (WMD = -2.70 pg/mL, 95%CI: -5.25, -0.16; p = 0.037), leptin (WMD = -1.58 ng/mL; 95%CI: -2.82, -0.35; p = 0.012), alanine transaminase (ALT) (WMD = 0.71 U/L; 95%CI: -0.31, 1.85; p = 0.164), triglyceride (TG) (WMD = -13.89 mg/dL; 95%CI: -20.69, -7.09; p < 0.001), total cholesterol (TC) (WMD = -2.26 mg/dL; 95%CI: -4.18, -0.34; p = 0.021), systolic blood pressure (SBP) (WMD = -1.29 mmHg; 95%CI: -2.44, -0.15; p = 0.027), and diastolic blood pressure (DBP) (WMD = 0.02 mmHg; 95%CI: -0.41, 0.45; p = 0.925) in an intervention group, compared with a placebo group. The non-linear dose-response analysis showed that ACB reduces the TC in trial duration by >50 weeks, and 180 mg/day is more effective for the decrement of CRP. ACB can improve lipid profiles, glycemic indices, anthropometric indices, and inflammatory markers in T2D, T1D, and IGT patients.

Effects of Metformin on COVID-19 Patients with Type 2 Diabetes: A Retrospective Study.

The pandemic of coronavirus disease 2019 (COVID-19) has highlighted the intricate relationship between underlying conditions and death. We designed this study to determine whether metformin therapy for type 2 diabetes mellitus (T2D) is associated with low in-hospital mortality in patients hospitalized for COVID-19. This was a retrospective study including patients with COVID-19 and T2D in Wuhan, from February 4th to April 11th, 2020. Patients were divided into two groups according to metformin exposure. The hazard ratio (HR) of COVID-19-related mortality and invasive mechanical ventilation was estimated using Cox regression. There were 571 T2D patients among the 4330 confirmed COVID-19 patients. Of those patients, 241 received metformin therapy. The in-hospital mortality and invasive mechanical ventilation of metformin group was lower than non-metformin group. In the multivariate model, metformin use was linked to a decreased in-hospital mortality and invasive mechanical ventilation when compared with that of the control group (HR: 0.376 [95% CI 0.154-0.922]; P = 0.033). Our study indicated that metformin therapy was associated with decreased death risk in COVID-19 patients with T2D.

Health-Related Quality of Life Assessment in Older Patients with Type 1 and Type 2 Diabetes.

Type 1 (T1D) and type 2 diabetes (T2D) are determinants of health-related outcomes including health-related quality of life (HRQOL). We aimed to determine differences in HRQOL between older adults with T1D and T2D and specific factors influencing HRQOL in this age group. This study used a cross-sectional design with 56 age- and HbA1c-matched T1D and T2D patients (aged 68.9 ± 7.8 years; 55% had T2D). We employed several validated questionnaires (Short Form-36 (SF-36) and the EuroQol-5 Dimensions/Visual Analog Scale (VAS)) to investigate the relationships between HRQOL domains and diabetes type, glycemic control, complications, and comorbidities. T1D was associated with better self-reported general health (assessed with the SF-36 general health domain (p = 0.048) and the EuroQol-5 VAS (p = 0.002), whereas no significant differences in the other SF-36 domains, self-reported diabetes distress, anxiety, or depression were found. Most HRQOL domains were not associated with HbA1c or the presence of diabetes complications. The most significant reduction in HRQOL was experienced by patients with higher BMIs, irrespective of the diabetes type. The obtained HRQOL data could be used in clinical settings for evidence-based patient education focused on specific subgroups of patients, as well as in national healthcare policies, e.g., interventions designed to alleviate obesity.

Physical activity patterns in type 1 diabetes in Spain: The SED1 study

AimsTo describe the physical activity (PA) frequency and intensity in the Spanish type 1 diabetes mellitus (T1D) population and its association with their glycemic control.MethodsA cross-sectional observational study was carried out in 75 Spanish public hospitals (the SED1 study). T1D patients over 14years of age self-completed the International Physical Activity Questionnaire (IPAQ) to determine their level of exercise. The relationship between PA frequency and intensity in T1D patients and glycemic control and the diabetes therapeutic education received were analyzed.ResultsA total of 592 patients were evaluable. A 6.8% of the sample performed light PA, 20.9% moderate and 72.3% vigorous. Estimated PA presented a high inter-individual variability. Men consumed more energy (METS) than women, these differences being more noticeable in vigorous METS (2865.80 in men vs 1352.12 in women). Women invested more min/week in the domestic and garden area (639.03 vs 344.39, p = 0,022). A correlation between glycemic control and the METs was not observed.ConclusionsThe Spanish T1D population performed PA in a higher frequency and intensity than the general population. A relationship between PA and glycemic control couldn´t be shown. However, limitations of the study should be kept in mind to discard a long-term positive influence.

From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures.

Background and aim-Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods-Thirty subjects, aged 45-65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results-Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions-The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations.

Effectiveness of flash glucose monitoring in patients with type 1 diabetes and recurrent hypoglycemia between early and late stages after flash glucose monitoring initiation

AimsEvaluate the effectiveness of reimbursed flash glucose monitoring with optional alarms (FGM) in preventing severe hypoglycemia (SH) and reducing hypoglycemia exposure in T1D patients prone to hypoglycemia. MethodsAmbispective study in T1D patients treated with multiple daily injections (MDI) and prone to hypoglycemia, initiating reimbursed FGM (FreeStyle Libre 2). The primary outcome was the number of SH events (requiring third party assistance) and main secondary outcomes were time below range < 70 (TBR < 70) and < 54 mg/dL (TBR < 54), impaired awareness of hypoglycemia (IAH) and quality of life (QoL). Logistic regression models were constructed to explore variables associated with success of the intervention. ResultsWe included 110 patients (52.7 % women, mean age 47.8 ± 17.0 years). SH events at 1-year follow-up decreased from 0.3 ± 0.6 to 0.03 ± 0.2 (p < 0.001). Significant reductions in patients presenting an SH (26.4 % vs. 2.9 %, p < 0.001) and IAH (47.1 % vs. 25.9 %, p = 0.002) were observed, as well as improvements in QoL. TBR < 70 and TBR < 54 were not significantly reduced. Baseline GMI was inversely associated with a decrease in TBR < 70 [OR 0.37 (0.15–0.93)] and directly with an increase in time in range 70–180 mg/dL [OR 2.10 (1.03–4.28)]. ConclusionsFGM decreased SH and improved hypoglycemia awareness and QoL. Initial tight glycemic control was associated with a decrease in hypoglycemia, while patients with suboptimal control reduced hyperglycemia.

Glucokinase and glucokinase activator

Abstract Glucokinase (GK) plays a pivotal role in glucose homeostasis as the glucose sensor in the pancreas and liver. Loss of function of GK results in hyperglycemia, and gain of function causes congenital hyperinsulinemic hypoglycemia. We speculate that the progressive loss of GK at both messenger RNA (mRNA) and protein levels in the islets and liver would be the key mechanism for Type 2 diabetes (T2D) pathogenesis. The development of GK activator (GKA) as an anti-diabetic drug has been endeavored for several decades. The failure of the early development of GKAs is due to the limitation of understanding the mode of GKA action. The success of dorzagliatin in the treatment of T2D has brought new hope for GK in setting a good model for repairing the underlying defects in the pancreatic islets and liver of T2D patients.