The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.

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Effect of Salivary Exosomal miR-25-3p on Periodontitis With Insulin Resistance

Frontiers in Immunology ◽

10.3389/fimmu.2021.775046 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jin-Seok Byun ◽

Ho Yeop Lee ◽

Jingwen Tian ◽

Ji Sun Moon ◽

Jaejin Choi ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

T Cells ◽

Immune Cells ◽

Γδ T Cells ◽

Healthy Individuals ◽

Local Inflammation ◽

Diet Induced Obesity ◽

Exosomal Mirna

Periodontitis is caused by an oral microbial dysbiosis-mediated imbalance of the local immune microenvironment, which is promoted by insulin resistance and obesity. The prevalence and severity of periodontitis is higher in patients with type 2 diabetes than in healthy individuals, possibly because of differences in immune responses. The level of glycemic control also affects the saliva profile, which may further promote periodontal disease in diabetes patients. Therefore, we compared the salivary exosomal miRNA profiles of patients with type 2 diabetes with those of healthy individuals, and we found that exosomal miR-25-3p in saliva is significantly enriched (by approximately 2-fold, p < 0.01) in obese patients with type 2 diabetes. We also identified CD69 mRNA as a miR-25-3p target that regulates both activation of γδ T cells and the inflammatory response. Knockdown of CD69 increased (by approximately 2-fold) interleukin-17A production of γδ T cells in vitro. To evaluate the role of exosomal miRNA on progression of periodontitis, we analyzed regional immune cells in both periodontal tissues and lymph nodes from mice with periodontitis. We found that diet-induced obesity increased the population of infiltrating pro-inflammatory immune cells in the gingiva and regional lymph nodes of these mice. Treatment with miR-25-3p inhibitors prevented the local in vivo inflammatory response in mice with periodontitis and diet-induced obesity. Finally, we showed that suppression of interleukin 17-mediated local inflammation by a miR-25-3p inhibitor alleviated (by approximately 34%) ligature-induced periodontal alveolar bone loss in mice. Taken together, these data suggest that exosomal miR-25-3p in saliva contributes to development and progression of diabetes-associated periodontitis. Discovery of additional miR-25-3p targets may provide critical insights into developing drugs to treat periodontitis by regulating γδ T cell-mediated local inflammation.

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Sociodemographic, anthropometric and physical fitness parameters in healthy individuals with and without family history of Hypertension and/ or Type 2 Diabetes Mellitus

Journal of Medical Science And clinical Research ◽

10.18535/jmscr/v5i8.02 ◽

2017 ◽

Vol 5 (8) ◽

Author(s):

Dr Shivani Agarwal ◽

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Family History ◽

Physical Fitness ◽

Healthy Individuals ◽

Fitness Parameters ◽

History Of ◽

Family History Of Hypertension

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The Association of Food Insecurity, Inflammation, and Several Socioeconomic Factors with Type 2 Diabetes: A Case-Control Study

Journal of Nutrition and Food Security ◽

10.18502/jnfs.v5i1.2317 ◽

2020 ◽

Author(s):

Hamideh Janzadeh ◽

Hassan Mozaffari-Khosravi ◽

Maryam Javadi

Keyword(s):

Type 2 Diabetes ◽

Food Insecurity ◽

Case Control Study ◽

Economic Status ◽

Case Control ◽

Diabetic Patients ◽

Healthy Individuals ◽

Household Food ◽

Control Study

Background: Considering that food insecurity can be a precursor to health and nutrition problems, determining its associated factors seems necessary in any society. The purpose of this case-control study was to determine the food insecurity, c-reactive protein (CRP), and some socio-economic factors in type 2 diabetic patients. Methods: The present study was conducted on 200 people with type 2 diabetes mellitus (T2DM) and 200 healthy individuals within the age range of 30 to 59 years. Food security was assessed using the US Department of Agriculture Household Food Security questionnaire. Anthropometric index, physical activity, and biochemical factors were measured by questionnaire and blood test. Results: The prevalence of food insecurity was 71% within the diabetic patients, of which, 65.5% had food insecurity without hunger, 3.5% had food insecurity with moderate hunger, and 2% had food insecurity with severe hunger. In addition, 24.9% of the participants were healthy. The level of fasting blood glucose and inflammatory factors (CRP, WBC) were significantly higher in food insecure participants compared to the healthy individuals (P < 0.05). Multivariate logistic analysis showed that food insecurity, BMI > 25, occupational status, economic status, and education level were significantly correlated with T2DM (P < 0.001). Conclusion: As a result, health care providers should take measures to reduce the food insecurity in the community, specifically within T2DM patients. To this end, the individuals' economic status should be improved and the household food patterns should be modified.

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Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?

Frontiers in Medicine ◽

10.3389/fmed.2021.712671 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dan Xu ◽

Owain Chandler ◽

Cleo Wee ◽

Chau Ho ◽

Jacquita S. Affandi ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Clinical Trial ◽

Diabetic Patients ◽

Atherosclerotic Cardiovascular Disease ◽

Healthy Individuals ◽

Type 2 Diabetic Patients ◽

Sodium Glucose Cotransporter ◽

Type 2 Diabetic

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively novel class of drug for treating type 2 diabetes mellitus (T2DM) that inhibits glucose reabsorption in the renal proximal tubule to promote glycosuria and reduce blood glucose levels. SGLT2i has been clinically indicated for treating T2DM, with numerous recent publications focussing on both primary and secondary prevention of cardiovascular and renal events in Type 2 diabetic patients. The most recent clinical trials showed that SGLT2i have moderately significant beneficial effects on atherosclerotic major adverse cardiovascular events (MACE) in patients with histories of atherosclerotic cardiovascular disease. In this review and analysis, SGLT2i have however demonstrated clinically significant benefits in reducing hospitalisation for heart failure and worsening of chronic kidney disease (CKD) irrespective of pre-existing atherosclerotic cardiovascular disease or previous heart failure history. A meta-analysis suggests that all SGLT2 inhibitors demonstrated the therapeutic benefit on all-cause and cardiovascular mortality, as shown in EMPAREG OUTCOME study with a significant decrease in myocardial infarction, without increased stroke risk. All the above clinical trial recruited type 2 diabetic patients. This article aims to postulate and review the possible primary prevention role of SGLT2i in healthy individuals by reviewing the current literature and provide a prospective overview. The emphasis will include primary prevention of Type 2 Diabetes, Heart Failure, CKD, Hypertension, Obesity and Dyslipidaemia in healthy individuals, whom are defined as healthy, low or intermediate risks patients.

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Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes?

Journal of Diabetes Research ◽

10.1155/2017/7583506 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Matthias Ploug Larsen ◽

Signe Sørensen Torekov

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Fasting Glucose ◽

Incretin Effect ◽

Nonesterified Fatty Acids ◽

Incretin Hormone ◽

Pubmed Database ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Background. The incretin effect is impaired in patients with type 2 diabetes. Aim. To assess the relation between the incretin hormone GLP-1 and the prediabetic subtypes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and the combined IFG/IGT to investigate whether a low GLP-1 response may be a predictor of prediabetes in adults. Method. 298 articles were found using a broad search phrase on the PubMed database and after the assessment of titles and abstracts 19 articles were included. Results and Discussion. Studies assessing i-IFG/IFG and i-IGT/IGT found both increased, unaltered, and reduced GLP-1 levels. Studies assessing IFG/IGT found unaltered or reduced GLP-1 levels. When assessing the five studies with the largest sample size, it clearly suggests a decreased GLP-1 response in IFG/IGT subjects. Several other factors (BMI, glucagon, age, and nonesterified fatty acids (NEFA)), including medications (metformin), may also influence the secretion of GLP-1. Conclusion. This review suggests that the GLP-1 response is a variable in prediabetes possibly due to a varying GLP-1-secreting profile during the development and progression of type 2 diabetes or difference in the measurement technique. Longitudinal prospective studies are needed to assess whether a reduced GLP-1 response is a predictor of diabetes.

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