Is “Leptin Resistance” Another Key Resistance to Manage Type 2 Diabetes?

2020 ◽  
Vol 16 (7) ◽  
pp. 733-749
Author(s):  
Juan Salazar ◽  
Mervin Chávez-Castillo ◽  
Joselyn Rojas ◽  
Angel Ortega ◽  
Manuel Nava ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Caloric Intake ◽  
Leptin Resistance ◽  
Low Grade ◽  
Leptin Sensitivity ◽  
Central Activity ◽  
Hypothalamic Inflammation ◽  
Treatment Of Obesity ◽  
Small Clinical Trials

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

scholarly journals Medicines for the Treatment of Obesity

2021 ◽  
Vol 22 (8) ◽  
pp. 3866
Author(s):  
Soon Shik Shin ◽  
Michung Yoon
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Disorders ◽  
Lifestyle Modification ◽  
Caloric Intake ◽  
Morbidly Obese ◽  
Treatment Of Obesity ◽  
The U.S

Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. In conjunction with obesity, related metabolic disorders, such as type 2 diabetes mellitus, dyslipidemia and hypertension, have become global health problems [1]. Reducing body weight by lifestyle modification is recommended, but drug intervention is necessary for morbidly obese individuals. Four drug therapies, including orlistat, naltrexone/bupropion, phentermine/topiramate and liraglutide, were approved for long-term use by the U.S. [...]

Chronic Low Grade Inflammation in Type 2 Diabetes—Activation of the Inflammasomes by Circulating Metabolites

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1726-P
Author(s):  
MARIE MONLUN ◽  
VINCENT RIGALLEAU ◽  
LAURENCE BLANCO ◽  
KAMEL MOHAMMEDI ◽  
PATRICK BLANCO
Keyword(s):  
Type 2 Diabetes ◽  
Low Grade ◽  
Low Grade Inflammation

scholarly journals Association between fasting insulin and C-reactive protein among adults without diabetes using a two-part model: NHANES 2005–2010

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amanda L. Missel ◽  
Laura R. Saslow ◽  
Dina H. Griauzde ◽  
Donna Marvicsin ◽  
Ananda Sen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Waist Circumference ◽  
Low Grade ◽  
Fasting Insulin ◽  
C Reactive Protein ◽  
Glucose Levels ◽  
Reactive Protein ◽  
Part Model

Abstract Introduction Chronic inflammation is associated with the development, progression and long-term complications of type 2 diabetes. Hyperglycemia is associated with chronic low-grade inflammation, and thus has become the focus of many screening and treatment recommendations. We hypothesize that insulin may also be associated with inflammation and may be an additional factor to consider in screening and treatment. Methods This study used National Health and Nutrition Examination Survey data from 2005 to 2010 to analyze the association between fasting insulin and C-reactive protein (CRP). A two-part model was used due to the high number of values reported as 0.1 mg/L. Two models were analyzed, both with and without the addition of waist circumference to other covariates in the model. Results The final sample included 4527 adults with a mean age of 43.31 years. In the first model, higher fasting insulin was associated with increased odds of CRP > 0.1 mg/L (OR = 1.02, p < .001) and with higher CRP (β = 0.03, p < .001). In the adjusted model, including waist circumference as a covariate, higher fasting insulin was not associated with CRP > 0.1 mg/L (OR = 1.00, p = .307) but the association between higher fasting insulin and higher continuous CRP remained significant (β = 0.01, p = .012). Conclusion This study found that higher fasting insulin is associated with higher CRP. These results suggest that treatment approaches that simultaneously decrease insulin levels as well as glucose levels may provide additive anti-inflammatory effects, and therefore may improve long-term outcomes for adults with type 2 diabetes.

C-reactive protein: a marker or a player?

2007 ◽  
Vol 113 (2) ◽  
pp. 79-81 ◽  
Author(s):  
Thomas Nyström
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Protein A ◽  
Low Grade ◽  
Phase Reaction ◽  
Clinical Markers ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp

It has been suggested that Type 2 diabetes may, in part, be precipitated or accelerated by an acute-phase reaction as part of the innate immune response, in which large amounts of cytokines are released from adipose tissue, creating a low-grade inflammatory milieu. There is also firm evidence that atherosclerosis is an immune-mediated inflammatory disease. Therefore it is reasonable to imply that low-grade inflammation is an important pathogenetic factor in atherosclerosis and cardiovascular events in patients with Type 2 diabetes. Over the last few years, there have been a lot of promising clinical markers proposed to link inflammation and atherosclerosis. Of these markers, hs-CRP (high-sensitivity C-reactive protein) might be a prognostic marker for further cardiovascular events, although this has been refuted recently. In this issue of Clinical Science, Castoldi and co-workers have demonstrated that, in patients with Type 2 diabetes categorized into low (<1.0 mg/l), medium (1.0–3.0 mg/l) and high (>3.0 mg/l) hs-CRP groups, serum levels of hs-CRP correlated with lipopolysaccharide-stimulated release of interleukin-1β and interleukin-6 in whole blood. This finding may indicate that low-grade inflammatory activity might influence cytokine production in these patients.

Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in Type 2 diabetes

2007 ◽  
Vol 24 (9) ◽  
pp. 969-976 ◽  
Author(s):  
A. M. W. Spijkerman ◽  
M.-A. Gall ◽  
L. Tarnow ◽  
J. W. R. Twisk ◽  
E. Lauritzen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Low Grade ◽  
Low Grade Inflammation
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