Biotechnological Assessment of SLC47A2 Genetic Variations and Glycemic Control in Diabetes Mellitus

Exercise training intervention represents an effective means to reduce adipose tissue mass, improve glycaemic control and increase whole-body oxygen uptake capacity (VO(2peak)) in obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM) and heart disease patients. In this manuscript, we review the impact of different exercise training modalities on clinical benefits of prolonged exercise intervention in these patient (sub)populations. By changing training modalities, significantly greater clinical benefits can be obtained. Greater training frequency and longer programme duration is associated with greater reduction in adipose tissue mass in obesity patients. A greater training frequency (up to 2 days/week) and a longer programme duration (up to 38 weeks) seems to be associated with greater improvements in VO(2peak) in heart disease patients. Longer programme duration and addition of resistance-type exercise further improve glycaemic control in T2DM patients. The first line of evidence seems to indicate that high-intensity interval exercise training has a greater impact on VO(2peak) in heart disease patients and insulin sensitivity in subjects with metabolic syndrome, but not on adipose tissue mass in obese subjects. However, it remains unclear whether addition of resistance-type exercise and continuous higher-intensity endurance-type exercise training are accompanied by greater improvements in VO(2peak) in heart disease patients. Furthermore, the impact of training session duration/volume on adipose tissue mass loss and glycaemic control in obesity and T2DM patients, respectively, is currently unknown. The impact of training frequency on glycaemic control remains to be investigated in T2DM patients.

High sensitivity C-reactive protein (Hs-CRP) is a sensitive marker of subclinical inflammation associated with atherosclerosis. Uncontrolled diabetes mellitus (DM) is one of the important risk factors of coronary heart disease (CHD). The aim of this study was to evaluate the association between Hs-CRP levels and both glycaemic control and CHD in Syrian type 2 diabetes mellitus (T2DM) patients. A random sample of 108 subjects was selected from T2DM and/or CHD patients seen in the National Centre for Diabetes, and the outpatient clinic of cardiology department at Tishreen University Hospital in Latakia. Four groups were formed: Group 1 [T2DM (+) CHD (-), N=29], Group 2 [T2DM (-) CHD (+), N=25], Group 3 [T2DM (+) CHD (+), N=29], and Group 4 (T2DM (-) CHD (-), N=25). Serum Hs-CRP and glycated haemoglobin (HBA1C) were determined. The SPSS 25.0 program was used for the statistical analysis. Probability (P) value less than 0.05 was considered statistically significant. Mean Hs-CRP level was higher in T2DM subjects with (5.23±1.56mg/l) or without (2.29±0.78mg/l) CHD compared to T2DM (-) CHD (-) patients (0.16±0.04mg/l), (p<0.0001 for both). Mean Hs-CRP level in T2DM with CHD was not only higher than T2DM patients without CHD (p<0.0001), but also than non-diabetic subjects with CHD (2.56±0.45mg/l) (p<0.0001). There was a positive correlation between serum Hs-CRP and HBA1C in T2DM patients with CHD (r=0.781, P<0.0001), Similarly, Hs-CRP levels were positively and significantly correlated with HBA1C in T2DM patients without CHD (r=0.800, p<0.0001). We also noticed that for every 1.0% increase in HbA1c there was an 77% increase in the likelihood of having an elevated Hs-CRP. We concluded that Hs-CRP was strongly correlated with glycaemic control in T2DM patients. The highest Hs-CRP level was observed in T2DM with CHD patients. Hs-CRP could predict the incidence of coronary heart disease in T2DM patients.

Background/Aim: Type 2 diabetes mellitus (T2DM) is a common chronic disease with an increasing incidence worldwide and its effects are being seen in many countries. Insulin resistance is the main factor in the pathophysiology. T2DM leads to an increase in mortality and morbidity due to macrovascular and microvascular complications. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are effective parameters in monitoring the inflammatory response. The primary aim of this study was to investigate glycemic control in patients with type 2 diabetes by focusing on their correlation with inflammatory markers, such as NLR and PLR, glycated hemoglobin (HbA1c), and fasting blood glucose levels. Methods: The present study was carried out in 2022 within the purview of the Internal Medicine Clinic at Balikesir İvrindi State Hospital. Data from the initial annual consultations of patients with T2DM, either newly diagnosed or previously diagnosed and visiting for follow-up, were utilized. Our study excluded patients under the age of 18 and those diagnosed with cirrhosis, heart failure, type 1 diabetes mellitus, malignancy, epilepsy, acute infection, pregnancy, or chronic inflammatory disease. We further excluded those on medications including steroids, antivirals, anticonvulsants, antipsychotics, antithyroids, and chemotherapeutic drugs that impact the leukocyte count. Based on their HbA1c levels, patients were systematically categorized into two distinct cohorts: those with controlled blood sugar (HbA1c ≤7%) and those with uncontrolled blood sugar (HbA1c >7%). In the ambit of this study, we incorporated data from 205 patients. We employed a cross-sectional study that retrospectively examined the correlation between NLR, PLR, and glycemic regulation in T2DM patients. SPSS 22.0 software was used to perform statistical calculations. Results: It was observed that patients with poor glycemic control had longer disease durations and this disparity bore statistical significance (P=0.005). Patients exhibiting poor glycemic control demonstrated elevated levels of CRP (C-reactive protein), a difference that reached statistical significance (P=0.003). The group exhibiting poor glycemic control demonstrated a notable elevation in NLR, indicating statistical significance (P=0.001). Although it was not statistically significant, PLR was found to be higher in patients with uncontrolled T2DM (P=0.441). Conclusion: This research investigates the correlation between HbA1c levels and inflammatory markers, specifically NLR and TLR, in T2DM patients who exhibit poor control of glycemia. Our findings highlight the potential of these markers as indicators of glycemic control, thus emphasizing the need for integrated strategies for managing inflammation and improving glycemic control in T2DM patients. The novelty of this area of research contributes to the scarcity of available literature, underlining the importance and timeliness of this study. Based on our findings, we suggest an increased focus on regular monitoring of inflammatory markers, for instance NLR and PLR, to assess the glycemic control in T2DM patients. The significant correlation of these markers with HbA1c levels implies that they could potentially serve as useful tools in personalizing diabetes management strategies, leading to improved patient outcomes. Not only does our research contribute to filling this knowledge gap, but it also underscores the potential for utilizing inflammatory markers in tracking disease progression and optimizing treatment efficacy in T2DM.

Purpose: To investigate the genetic polymorphisms that may contribute to the worsening of glycemic control in type 2 diabetes mellitus (T2DM) with severe or acute hyperglycemia.Methods: The prospective cohort study included 156 T2DM patients with severe or acute hyperglycemia from all medical wards of the National University of Malaysia Medical Centre (UKMMC) that were treated with insulin therapy. For the genetic association study, we used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The glycemic control assessment during the acute phase was based on the degree to which the patient achieved the targeted glucose levels. The primary outcome was the influence of IRS gene on glycemic control in T2DM patients with severe/acute phase hyperglycemia.Results: Insulin Receptor Substrate 1 (IRS1) (R2 = -0.023, p = 0.771) and Insulin Receptor Substrate 2 (IRS2) gene polymorphisms (R2 = -0.160, p = 0.046) were not associated with glycemic control in T2DM patients with severe/acute hyperglycemia.Conclusion: The IRS1 and IRS2 genetic factors may not be significant genetic determinant for glycemic control in T2DM patients during severe/acute phase hyperglycemia.Keywords: Insulin receptor substrate, Gene, Polymorphism, Diabetes, Insulin resistance,Hyperglycemia, IRS 1, IRS 2

BACKGROUND: Glycemic control is essential in managing type 2 diabetes mellitus (T2DM) to reduce the risk of complications, including diabetic nephropathy. Traditionally, glycated hemoglobin (HbA1c) has been the gold standard for assessing long-term glycemic control. However, glycated albumin (GA) has emerged as a potential alternative due to its shorter lifespan and reduced sensitivity to erythrocyte lifespan changes. AIMS AND OBJECTIVES: This study aimed to compare the efficacy of GA and HbA1c in evaluating glycemic control in stable T2DM patients, particularly regarding its implications for diabetic nephropathy and associated complications. METHODOLOGY: A comparative analysis was conducted between GA and HbA1c levels in a cohort of stable T2DM patients. The primary focus was on assessing the reliability and clinical applicability of GA as a marker for glycemic control, especially in cases where HbA1c might provide misleading results. RESULTS: The study findings indicated that GA could offer a valuable alternative for glycemic monitoring, especially in clinical scenarios where HbA1c might not accurately reflect glycemic status due to erythrocyte lifespan variations. The use of GA could enhance the precision of glycemic control assessment, thus potentially improving patient care. CONCLUSION: The results underscore the importance of incorporating GA in clinical practice as an adjunct to HbA1c, particularly in situations where HbA1c may be unreliable. GA provides a promising alternative for better management of glycemic control in T2DM patients, potentially impacting the management and progression of diabetic nephropathy.

Background: The aim of this study was to assess the association of triglyceride-glucose (TyG) index with glycated haemoglobin (HbA1c) and insulin resistance in type 2 diabetes mellitus (T2DM). Methods:A total of 140 patients with T2DM were included in this cross-sectional study and divided into two groups according to their HbA1c levels: participants with HbA1c <7.0% (n=75) and those with HbA1c >7.0% (n=65) were defined as having a good glycemic control (group I) and a poor glycaemic control (group II) in T2DM. Anthropometric and biochemical parameters were measured, while the values of triglyceride (TG) to high density lipoprotein cholesterol (HDL-C) (TG/HDL-C) ratio and TyG index were calculated using formula. Results: Body mass index (BMI), fasting blood glucose (FBS), HbA1c and homeostatic model assessment for insulin resistance (HOMA-IR) were significantly higher in diabetic patients with poor glycemic control. TyG index was significantly correlated with HbA1c, HOMA-IR, TyG-BMI and TyG-WC. The receiver operating characteristic (ROC) analysis showed that TyG had a maximum area under the curve of 0.806, with a cut off value of 15.5 for identifying glycemic control in diabetic patients. Conclusion:TyG index is a useful tool for assessing glycemic control in T2DM patients and positively correlated with HbA1c and HOMA-IR. Hence, TyG can be used as a simple and inexpensive alternative to assess glycemic control in patients with diabetes.

Diabetes mellitus (DM) and thyroid dysfunction (TD) often tend to coexist in patients. Both hypothyroidism and hyperthyroidism are more common in type 2 diabetes mellitus (T2DM) patients than in their nondiabetic counterparts. Current guidelines are neither clear nor specific about the frequency of thyroid function monitoring in T2DM patients. Circulating thyroid hormones affect several different organs and cells, have a major impact on glucose, lipid, and protein metabolism, and can worsen glycaemic control in T2DM. Hyperthyroidism and thyrotoxicosis can worsen subclinical DM and cause hyperglycaemia in T2DM patients, increasing the risk of diabetic complications. T2DM reduces thyroid-stimulating hormone levels and impairs the conversion of thyroxine (T4) to triiodothyronine (T3) in the peripheral tissues. Poorly managed T2DM can lead to insulin resistance and hyperinsulinaemia, which causes thyroid tissue proliferation and increases nodule formation and goitre size. In addition, while metformin can be beneficial in both T2DM and TD patients, other antidiabetics such as sulfonylureas, pioglitazone, and thiazolidinediones can negatively impact TD. Antithyroid drugs such as methimazole can impair glycaemic control in T2DM patients. Thyrovigilance in T2DM patients and diabetovigilance in TD patients may therefore be necessary to facilitate individualized care and management.Funding: Abbott India Ltd.

Subclinical hypothyroidism (SCH) as mild thyroid disorder or comorbidity in patients with endocrine disorders is closely related with insulin resistance (IR) and poor glycemic control. The present study attempted to investigate the effect of SCH on IR and glycemic control in patients with type 2 diabetes mellitus (T2DM). In addition, the effects of ellagic acid (EA) on SCH C57BL/6J and db/db mice were also investigated to explore potential therapeutic drug against SCH-induced abnormal glucose metabolism. T2DM patients were recruited in our study and categorized into two groups accordingto thyroid stimulating hormone (TSH) value: T2DM without SCH group (TSH ≤4μIU/ml; n=30) and T2DM with SCH group (TSH >4μIU/ml; n=60). Methimazole (MMI; 0.08mgkg-1 day-1 ) was intragastrically administrated for 12weeks to establish SCH in C57BL/6J and db/db mice. Compared with T2DM patients without SCH, poor glycemic and cholesterol control were emerged in T2DM patients with SCH and that were prominent in patients with TSH more than 10μIU/ml. In addition, a significant positive correlation between serum TSH and fasting plasma-glucose (FPG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), or glycated hemoglobin (HbA1c) was observed in T2DM patients with SCH. Moreover, abnormal glucose metabolism in C57BL/6J and db/db mice with SCH has been attenuated by EA administration. Our findings provided data regarding the positive correlation between high TSH level with poor glycemic control in T2DM patients with SCH. EA might be a supportive strategy for preventing SCH-induced abnormal glucose metabolism. PRACTICAL APPLICATIONS: Subclinical hypothyroidism (SCH) is a potential risk factor associated with abnormal glucose metabolism in patients with type 2 diabetes mellitus (T2DM). A clinical theory of a positive correlation between high TSH level and poor glycemic control was validated in type 2 diabetes mellitus patients and mouse models. Ellagic acid (EA) might be a supportive strategy for preventing SCH-induced abnormal glucose metabolism that provided a treatment option in T2DM patients with subclinical hypothyroidism in clinical practice.

Background: Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance and hyperglycemia. Iron metabolism disturbances, reflected by elevated serum ferritin levels, have been implicated in the pathogenesis and complications of T2DM. This study aimed to evaluate the clinical correlation between iron storage markers and glycemic control in T2DM patients at a tertiary care hospital. Methods: A cross-sectional observational study was conducted on 100 participants, including 50 diagnosed T2DM patients and 50 age- and gender-matched healthy controls. Parameters measured included glycated hemoglobin (HbA1c) and serum ferritin levels. Statistical analysis was performed to compare groups and assess correlations. Results: T2DM patients showed significantly higher mean HbA1c (8.2 ± 1.5%) and serum ferritin levels (150.6 ± 45.3 ng/mL) compared to healthy controls (HbA1c: 5.4 ± 0.6%, ferritin: 85.2 ± 30.7 ng/mL; p &lt; 0.001 for both). The body mass index (BMI) was also significantly greater in the diabetic group (28.4 ± 4.2 kg/m² vs. 23.9 ± 3.1 kg/m², p = 0.001). A moderate positive correlation was observed between serum ferritin and HbA1c levels, indicating a link between iron overload and poor glycemic control. Conclusion: Elevated serum ferritin levels are significantly associated with poor glycemic control in T2DM patients, suggesting that iron overload may contribute to disease progression. Monitoring serum ferritin alongside HbA1c could improve diabetes management. Further longitudinal studies are warranted to establish ferritin as a predictive biomarker in T2DM.

Type 2 Diabetes Mellitus, Glycemic Control, Inflammatory Markers, CRP, IL-6, HOMA-IR, Serum Insulin, BMI, Triglycerides, HDL-C Abstract Background: Type 2 Diabetes Mellitus (T2DM) is a growing global health concern characterized by chronic hyperglycemia due to insulin resistance and/or impaired insulin secretion. Inflammatory markers and metabolic parameters are increasingly recognized as important contributors to disease progression and glycemic control. Objective: To assess the relationship between blood glucose levels, serum insulin, inflammatory markers (CRP, IL-6), and metabolic parameters (BMI, lipid profile) in predicting glycemic control among patients with T2DM. Methods: This observational analytical study was conducted at the Department of Biochemistry and Department of General Medicine, Manipal College of Medical Sciences, Nepal. A total of 129 T2DM patients aged 30–65 years were included based on specific inclusion and exclusion criteria. Participants were categorized into good (HbA1c &lt; 7%) and poor (HbA1c ≥ 7%) glycemic control groups. Biochemical and metabolic markers were measured and statistically compared between groups. Results: Patients with poor glycemic control had significantly higher levels of fasting blood glucose, postprandial glucose, serum insulin, HOMA-IR, CRP, IL-6, BMI, and triglycerides (p &lt; 0.05). Conversely, HDL-C levels were significantly lower in this group. These findings indicate strong associations between poor glycemic control and increased insulin resistance, systemic inflammation, obesity, and dyslipidemia. Conclusion: Inflammatory and metabolic markers are significantly associated with poor glycemic control in T2DM patients. Monitoring these parameters may help in early detection of poor metabolic status and in guiding personalized treatment strategies to improve long-term diabetes outcomes.

Highlights1. The occurrence of macrovascular and microvascular problems is strongly associated with high mortality in type 2 diabetes mellitus (T2DM).2. Combinations of rapid-acting and long-acting insulin were the most frequent kind of insulin. AbstractBackground: High mortality in type 2 diabetes mellitus (T2DM) has a strong correlation with the presence of macrovascular and microvascular complications. The risk of these complications can be reduced through good glycemic control. As the disease progresses, patients may need to add or switch to insulin therapy rather than oral antihyperglycemic drugs to achieve desirable glycemic control. Objective: To determine the pattern of insulin therapy and glycemic control in T2DM patients. Material and Method: Data for this study were obtained from the medical records of the Diabetes Outpatient Clinic at the Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. This study was an observational descriptive. In June-July 2016, total samples were collected from 124 patients who received insulin therapy between February 2015 and March 2015. Result: According to the data obtained, the most commonly used insulin was a combination of rapid-acting and long-acting insulin (75.8%). While basal bolus insulin (75.8%) accounts for the most common regimen used to administer insulin, only 27.4% and 45% of total patients achieved good glycemic control based on FPG and PPG testing, respectively. HbA1c testing was done on 44 out of 124 people, with 9 people (20.5%) met the target of HbA1c &lt;7%. Conclusion: Glycemic control in T2DM patients who received insulin therapy was relatively low.

Type 2 diabetes mellitus (T2DM) patients have a raised risk of developing depression compared with non-diabetic people. The objective of this meta-analysis was to investigate the impacts of exercise training interventions to improve psychosocial aspects and glycemic control in T2DM patients. PubMed, CINAHL, Medline, Google Scholar, and Scopus databases and reference lists of included studies were searched. The selection criteria were randomized controlled trials (RCTs) using an exercise intervention with or without dietary advice on psychological aspects and glycemic control in T2DM patients, up to January 2021. Meta-analyses were performed using the random-effects model. The analysis included 17 RCTs with 2,127 participants. In the pooled analysis, improvements were seen in depression, standard mean difference (SMD) -0.65 (95% confidence interval (CI) -1.03 to -0.28, p = 0.0006), mental health SMD: 0.53 (95% CI 0.31 to 0.76, p < 0.00001), and HbA1c, weighted mean difference (WMD) -0.51% (95% CI -0.97 to -0.04, p = 0.03). There were no significant differences between the intervention and control groups for bodily pain, social functioning, and fasting glucose (all p > 0.05). Our systematic review and meta-analysis displayed that exercise training interventions decreased depression and HbA1c and increased mental health in individuals with T2DM. Further longer-term and high-quality clinical trials are required to additional assess and confirm the findings presented here.

BackgroundGood glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM) patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established.PurposeThis study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD).Patients and methodsThis retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C) was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7%) or poor glycemic control (A1C ≥7%) based on the recommendations of the American Diabetes Association.ResultsMajority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9%) was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and retinopathy (P=0.033), concurrent medications such as erythropoietin therapy (P=0.047), α-blockers (P=0.033), and antigouts (P=0.003) were also correlated with A1C.ConclusionIdentification of factors that are associated with glycemic control is important to help in optimization of glucose control in T2DM patients with renal complication.

Effects of synbiotics surpass probiotics alone in improving type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

AimTo compare the blood glucose control of patients with type 2 diabetes mellitus (T2DM) with different treatment methods, oral hypoglycemic agents (OHA) monotherapy, insulin injection and combined therapy (OHA + insulin injection) and evaluate their satisfaction with the medical care.MethodsA total of 1512 T2DM patients were assessed, to compare the effects of different treatment methods on glycemic control in T2DM patients, the influencing factors of patients’ satisfaction with medical care measures and their relationship with glycemic control. Fasting plasma glucose (FPG), 2 hrs postprandial plasma glucose (2hPG) and HbA1c were measured as the standard of the glycemic control. Satisfaction was defined using the simplified version of DAWN of chronic disease care patient scale (PACIC - DSF).ResultsIn this study, the FPG compliance rate, 2hPG compliance rate and HbA1c compliance rate were 25.5%, 22.7% and 19.5%, respectively. The differences in the glycemic control compliance rates of different treatment methods were not statistically significant. The total score of PACIC - DSF was 34.54±11.65(p>0.05), and the influencing factors included fast blood glucose (FBG) and 2hPG, 2hPG and PACIC - DSF were negatively correlated.ConclusionsThe T2DM glycemic control rate in China is currently low. From the score of the PACIC - DSF, there is no significant difference in general satisfaction with medical care measures in different treatments. What is more, education level, occupation and exercise of patients with type 2 diabetes had influence on PACIC - DSF score. Different treatment methods have no influence on the glycemic control of patients with T2DM. FPG value and the 2hPG value are negative correlation with the satisfaction of patients in medical care measures.