Professor Zou Dajin: Eliminating insulin resistance and removing the "common soil" of chronic diseases

Introduction: Since Hinsworth first reported the clinical phenomenon of insulin resistance (IR) in the 30s of the 20th century, human understanding of IR has been more than 90 years
.
In addition to diabetes, IR is currently found to be a "common soil"
that causes many chronic diseases.

With the deepening of research, people's understanding of IR has made great progress
.
So, regarding the prevention and treatment of IR, what aspects should the clinic start from? On this topic, Yimaitong is honored to invite Professor Zou Dajin from the Tenth People's Hospital Affiliated to Tongji University to share clinical diagnosis and treatment suggestions
.

Introduction by experts

Professor Zou Dajin

• Professor, Chief Physician and Doctoral Supervisor of the Tenth People's Hospital Affiliated to Tongji University;

• Honorary Director of Institute of Obesity, School of Medicine, Tongji University;

• Director of Shanghai Research Center for Metabolic and Thyroid Diseases;

• In 2017, he was the first famous doctor of the country;

• Vice President of the 1st to 4th Endocrinology and Metabolism Physician Branch of Chinese Medical Doctor Association;

• The first chairman of the Obesity Professional Committee of the Chinese Medical Doctor Association;

• Vice Chairman of the 6th, 7th and 8th Diabetes Branch of the Chinese Medical Association;

• The first leader of the obesity group of the Diabetes Branch of the Chinese Medical Association;

• The second and third deputy editors of the Chinese Journal of Diabetes, the sixth deputy editor of Shanghai Medicine;

• He is currently the former chairman of the Diabetes Association of Shanghai Medical Association;

• Vice Chairman
  of Endocrinologist Branch of Shanghai Medical Doctor Association.
  

Human understanding of "insulin resistance" began more than 90 years ago

IR refers to the fact that human liver cells, muscle cells, fat cells, islet cells, etc.
lose their normal glucose intake response to insulin and cannot obtain glucose in the blood, resulting in an increase
in blood sugar levels.
Due to the significantly reduced hypoglycemic effect of insulin, the islet β cells need to produce more insulin to lower blood sugar, and the islet function is progressively deteriorated, and the vicious circle of IR and hyperinsulinemia, hyperglycemia, and islet function decline occurs
.

Disease Awareness Process:

➤ In the 2030s, Hinsworth first reported the clinical phenomenon of IR;

➤ In the 50s of the 20th century, Yallow first proposed the concept of IR and hyperinsulinemia and won the Nobel Prize;

In the 80s of the 20th century, Reaven reported a group of closely related syndromes called IR syndrome or metabolic syndrome;

➤ In 1995, Stem proposed IR's "common soil" doctrine;

➤In the 21st century, a large number of research papers on the etiology, pathogenesis, harm and treatment of IR have been published, and in recent years, IR has gained a deeper understanding and understanding, and some new drugs
have been produced.

Insulin resistance is the "common soil" for many chronic diseases

Professor Zou Dajin pointed out that as China enters an aging society, physiological changes caused by aging, more concomitant diseases, insufficient exercise, and central obesity can lead to IR, and the prevalence of type 2 diabetes in the elderly increases
.
IR and associated hyperinsulinemia and chronic low-grade inflammation are important causes of obesity, hypertension, dyslipidemia, and increased risk of cardiovascular disease, and also increase the difficulty
of hypoglycemic therapy.
Therefore, the prevention and treatment of IR, the "common soil" of chronic diseases, is particularly important
.

Figure 1 Insulin resistance is the common soil of hyperglycemia and many metabolic disorders

Eradicate the "common soil" of chronic diseases and pay attention to the prevention and treatment of IR

Professor Zou Dajin pointed out that to eradicate IR, the "common soil" of chronic diseases, it is necessary to start
from several aspects such as lifestyle and drug intervention.

First, lifestyle intervention is the cornerstone of the prevention and treatment of IR

➤ Emphasis on healthy lifestyles: A study in Daqing, China, showed that lifestyle interventions for 6 years reduced the cumulative risk of type 2 diabetes by 43%
over the next 14 years.
A healthy lifestyle includes proper exercise, dietary changes, total calorie control, smoking cessation, and alcohol restriction
.

➤ Weight loss: Maintaining an ideal weight, for every 7% reduction in body mass index, the risk of developing type 2 diabetes is reduced by 58%.

The diabetes remission clinical trial (DiRECT study) showed that for patients with type 2 diabetes with a short course and obesity, the rapid weight loss with a low-calorie (825~853 kcal/d) diet led to a 1-year remission rate of diabetes mellitus of 46% (the remission rate of the control group was 4%), and the 2-year remission rate of 1>0 kg of weight loss reached 64%.

The key to successful mitigation is not only weight loss, it is more important to maintain the weight loss, while relieving IR;

With a weight loss of 10%~15%, most patients can get diabetes relief
.
Another study of non-obese but overweight diabetic patients found that weight loss through strict dietary control led to the majority of patients achieving diabetes remission
.
Professor Roy Taylor believes that even if the body mass index is relatively overweight, weight loss can still help reduce fat in the pancreas, liver and even muscle tissue, which is the same
mechanism by which weight loss induces IR remission in obese type 2 diabetic patients.

➤ Other life details: There are also life details that can help relieve IR, including regulating the intestinal flora, keeping the mouth clean, getting a good night's sleep, and reducing various stressors
.

2.
Drug intervention

With the deepening of research, in recent years, there has been a deeper understanding of IR, and new therapeutic drugs
have been produced.

1.
It can be used for drugs without diabetes and diabetic abdominal obesity

Studies have shown that hodan tablets, berberine and gastrointestinal lipase inhibitor orlistat has a certain effect
on the prevention and treatment of IR.

2.
Drugs used to treat type 2 diabetes mellitus with IR (hypoglycemic sensitizing drugs)

➤Thiazolidinediones (TZD): activates the nuclear transcription factor peroxidase proliferator activation receptor (PPAR) γ, promotes adipocyte differentiation, reduces fat ectopic deposition, and exerts IR relief and long-lasting hypoglycemic effects
.
Rosiglitazone is less used clinically due to more adverse reactions; Pioglitazone 45 mg can improve insulin sensitivity by 27%, have a certain triglyceride lowering effect
.

➤Metformin: reduce the output of liver glucose, improve peripheral IR, increase insulin sensitivity by 20%, and the maximum effective dose is 1.
5~2.
0 g/d
.

➤TZD and metformin fixed combination preparation (FDC): pioglitazone/metformin FDC can significantly reduce fasting insulin levels, increase HDL-C, and reduce triglyceride levels; The detection of hyperinsulin n-glucose clamping technology showed that pioglitazone combined with metformin increased insulin sensitivity by 53%, which was significantly higher than that of pioglitazone and metformin monotherapy group (27% and 20%), and had a synergistic effect
.
Pioglitazone and metformin FDC reduced HbA1c by 1.
58%~2.
78%, and blood sugar control was more durable
.

➤Dipeptidyl peptidase IV.
inhibitor (DPP-4i) and metformin FDC: compared with metformin treatment HbA1c decreased more significantly, HbA1c <7% rate was higher (49.
2% vs.
34.
2%), body weight decreased by 1.
6 kg, IR improvement was more obvious, the incidence of hypoglycemia was not significantly increased, and the incidence of diarrhea and abdominal pain was significantly lower than that in metformin group
.

➤Pan-PPAR agonist: siglitasodium can simultaneously activate PPARγ/δ/α three subtypes, which have the effects
of insulin sensitization, lowering blood sugar, reducing triglyceride and free fatty acid levels, and reducing fat ectopic deposition.
In two phase III clinical trials, the administration of siglitasodium 48 mg/day in patients with IR (HOMA-IR>3 or body mass index >25 kg/m^2 or elevated triglycerides and/or HDL-C decreased) reduced HbA1c by 1.
5% while relieving IR; Edema and weight gain were significantly reduced compared with TZD drugs, and the risk of heart failure was not increased
.

3.
Drugs used to treat type 2 diabetes mellitus with IR (hypoglycemic and weight-reducing drugs)

➤ Glucagon-like polypeptide-1 receptor agonist (GLP-1RA): plays a role in all aspects of IR occurrence, including appetite suppression, reduce energy excess, and reduce fat accumulation; Upregulate adiponectin levels, reduce free fatty acid levels, and reduce inflammatory cytokine levels; Increase the expression levels of glucose transporter-4 and hepatic fibroblast growth factor-21 in liver/skeletal muscle; Activation of intracellular adenosine monophosphate activates protein kinase levels, improves peripheral IR
.

➤GLP-1RA and basal insulin combination preparation: (a) Insulin glargine risnatide combination preparation: A 24-week randomized, open-label, three-arm, multicenter Chinese phase III study showed that the treatment with insulin glargine risnatide combination preparation in patients with type 2 diabetes mellitus with poor oral drug control reduced HbA1c by 1.
9%, and the improvement of body weight, triglycerides, HDL-C and IR was better than that of insulin glargine and risnatide alone; (b) Liraglutide/insulin degludec combination preparation 1 time / d injection, strong control of blood glucose throughout the day, for 32 weeks of treatment of patients with type 2 diabetes who did not meet the standard with oral hypoglycemic drugs alone, the standard compliance rate of HbA1c<7% was 89.
9%.

Reduces the risk of hypoglycemia and has a clear
weight benefit.
It is mainly used in patients
with mixed etiologies with both insufficient insulin secretion and IR.

➤Sodium-glucose co-transporter 2 inhibitor (SGLT2i): reduces the reabsorption of glucose in the renal tubules, excludes excess glucose, reduces excess energy, promotes the decomposition of fat into ketone bodies, reduces excessive secretion of insulin, reduces visceral fat, and reduces weight by 3 kg, thereby reducing IR throughout the
body.
SGLT2i also regulates fat and systemic metabolism and IR by reversing brain IR
.

➤SGLT2i and metformin FDC: can synergistically lower glucose, while reducing weight, blood pressure, and lowering uric acid
.
The treatment of empagliflozin and metformin FDC twice / day for 24 weeks can reduce HbA1c by 1.
9%~2.
1% (baseline HbA1c 8.
6%~8.
9%), HbA1c<7% compliance rate, weight loss of >5%, and the proportion of patients with HOMA-IR reduction are better than empagliflozin or metformin monotherapy
.

➤α-glycosidase inhibitors (AGIs): Studies on Chinese have shown that acarbose (300mg/d) has more weight loss, more significant triglyceride reduction, and improved intestinal flora than metformin (1500mg/d), suggesting a better effect
on improving insulin sensitivity.

4.
3 or 4 drugs in combination

➤SGLT2i with metformin FDC+GLP-1RA or GLP-1RA and basal insulin combination preparation: A cohort study published by Danish academics showed that this combination therapy was more effective than other combination regimens in relieving IR, significantly reducing the occurrence of major cardiovascular diseases and all-cause mortality, and had the lowest
risk of hypoglycemia.

➤ TZD and metformin FDC+GLP-1RA or GLP-1RA/basal insulin combination formulation: It was found that initiating intensive lifestyle intervention + triple therapy for newly diagnosed type 2 diabetes with significant IR resulted in a greater reduction in IR than the guideline recommended step therapy, resulting in a 5.
8%
HbA1c <.

3.
Metabolic bariatric surgery

For patients with type 2 diabetes mellitus who do not respond to lifestyle and pharmacological interventions and have a body mass index of > 32.
5 kg/m^2 to alleviate severe obesity-driven IR.

4.
Prevention of cardiovascular events

In a prospective cohort study of 111765 adults, patients with prediabetes or diabetes with ≥ 5 desirable markers of cardiovascular health had a lower or no significant additional risk
of cardiovascular events compared with those with normoglycemic conditions.
To this end, we advocate the whole people to achieve the following 7 ideal cardiovascular health indicators to do a good job in the prevention of cardiovascular events:

➤ Do not smoke or quit smoking for > 12 months;

➤Body mass index<23 kg/m^2;

➤Physical activity≥ moderate intensity physical activity of 150 min/week, or vigorous intensity physical activity of ≥75 min/week or moderate + vigorous physical activity of ≥150 min;

➤ Salt intake< 6 g/d;

➤Total cholesterol< 4.
5 mmol/L (untreated);

➤ Blood pressure< 120/80 mmHg (untreated);

➤ Ideal HbA1c (prediabetes <5.
7% or diabetes <6.
5%)
.

Disclaimer: This platform is designed to deliver more medical information
to healthcare professionals.
The content published on this platform cannot replace professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice
.
If such information is used for purposes other than understanding medical information, this platform does not assume relevant responsibilities
.
The content published by this platform does not mean that it agrees with its description and views
.
If copyright issues are involved, please contact us and we will deal with
it as soon as possible.