Edited by Yimaitong, please do not reprint without authorization. Introduction: The number of people with type 2 diabetes worldwide has increased dramatically over the past four decades. The number of patients jumped from 108 million in 1980 to 422 million in 2014, with the fastest growth in low- and middle-income countries, according to the World Health Organization. There are studies showing that middle-aged men seem to be more likely to develop diabetes than women, and the gender differences behind have aroused people’s curiosity.
Is the cause of diabetes different in men and women?
When it comes to the cause of diabetes, obesity is a topic that cannot be avoided.
Is there a gender difference in obesity? Do these differences affect the onset of diabetes?
Some scholars have conducted in-depth research on this topic. The research results were published in the academic journal OBESITYREVIEWS (IF: 9.213).
Possible mechanism of obesity-induced type 2 diabetes
Possible mechanism of obesity-induced type 2 diabetes, It can be summed up in the following figure.
Note: Dotted lines indicate secretions; solid lines indicate effector pathways
Figure 1 Obesity-induced type 2 diabetes. Possible Mechanisms
1. Method of adipogenesis
< /strong>Increases in free fatty acids (FFA) in the blood stimulate lipogenesis. Adipocytes can be generated either by cell proliferation, reduces insulin resistance, or by hypertrophy (increased apoptosis, inflammation, damage to adipocyte precursors), increased insulin resistance (Figure 1A).
2. Changes in adipokines
adipokines Secreted from adipose tissue into the blood. Elevated leptin levels in obese individuals impairs liver insulin sensitivity. In the pancreas, increased leptin levels reduce insulin secretion and exacerbate β-cell dysfunction;
Reduced adiponectin levels in obese individuals impair insulin receptors and IRS-1, also resulted in increased intramuscular lipid deposition and decreased insulin signaling in the pancreas, thereby increasing insulin resistance (Fig. 1B).
3. Changes in cytokines
With the increase of immune cell infiltration, fat Cytokine secretion by tissues is increased.
TNFα reduces the insulin receptor and its substrate IRS-1, and TNFα and IL6 together increase the secretion of C-reactive protein (CRP) in the liver. Increased cytokines stimulate inflammatory pathways, such as JNK and NF-κB in liver and skeletal muscle, increased insulin resistance. Elevated levels of CRP further impair the leptin signaling pathway (Fig. 1C).
4.Immune cells
Pro-inflammatory adipose tissue macrophages (ATM) in adipose tissue in obese subjects , Th cells and cytotoxic T cells increased, and anti-inflammatory Treg decreased, resulting in increased insulin resistance (Fig. 1D).
Gender differences in diabetes onset as ‘fat storage locations’
Diabetes is strongly associated with abdominal fat, as in many other diseases. However, there are significant differences between men and women when it comes to where fat is stored.
Although it’s all belly fat, women are more likely to store fat under the skin, so-called subcutaneous fat; while men’s belly fat tends to be Stored around organs, visceral fat. The latter is more closely related to the onset of diabetes.
Gender differences in “fat production”
Fat shows different characteristics in men and women: Differences in how inflammation and the immune system interact.
For example, In men, adipose tissue “expands” because of fat cell hypertrophy (in a way that increases insulin resistance); reduces insulin resistance).
This disappears as levels of the protective sex hormone estrogen drop after menopause, a change that may explain why men are more prone to diabetes than women.
Gender differences in “adipokines” and “cytokines”
The study found that with the progression of obesity, regional adipokines and cytokine release occurred changes in type 2 diabetes risk.
In men, TNFα levels were higher; while in women, leptin, CRP, and adiponectin levels were higher.
Gender-differentiated “immune cells”
The study found that regardless of gender, regional immune cell infiltration brought pathogenicity.
In obese men, there were more visceral adipose tissue-macrophages (VAT-ATM) and fewer protective Treg cells; in women, subcutaneous adipose tissue-macrophages (SAT-ATM) ) and more T cells.
Exploration of “Gender-Individualized Treatment Strategies”
Currently, the treatment of diabetes is similar for men and women. Some scholars said that in the future, we should have a deeper understanding of the differences in the occurrence and development of diabetes between different genders, and recommend more individualized treatment methods for patients.
References:
[1]KerriZ.Delaney,SylviaSantosa.SexdifferencesinregionaladiposetissuedepotsposedifferentthreatsforthedevelopmentofType2diabetesinmalesandfemales.ObesityReviews,2022;23(3)DOI:10.1111/obr.13393
[2]ConcordiaUniversity.”Originsofdiabetesmaybedifferentinmenandwomen:Developmentofthediseasedependsonlocationandfeaturesoffattissueineachsex.”ScienceDaily.ScienceDaily,23March2022.
