Current status and progress in the treatment of simple obesity

锘?

Current status and progress in the treatment of simple obesity

The US Health and Nutrition Survey of 1988-1994 showed that obese patients (body mass index 30 kg / m2) accounted for 20% of adult men and 24 of women.

9%.

The problem of severe obesity, represented by China, is also becoming more and more serious. The National Nutrition Survey in the 1990s showed that adults were overweight.

4%, obesity accounted for 3.

01%.

銆€銆€As the incidence of obesity spreads with the trend of epidemics, more and more evidence suggests that simple obesity and its related complications such as type 2 diabetes, hypertension, cardiovascular and cerebrovascular diseases and some tumorsThe occurrence of great harm to human health, prevention and treatment of obesity has become a global challenge.

Fortunately, studies have confirmed that when obese patients reduce their body weight by 5%?
More than 10%, obesity-related complications include high blood pressure, high blood sugar, high blood lipids and other serious problems to improve or even reverse.

銆€銆€Dietary and behavioral therapy is the cornerstone of obesity treatment. It shows that in the population, metabolic syndrome caused by single-gene mutations causes only a very small number of metabolic disorders. Simple obesity is in the genetic background of multiple genes, and moreIt is the result of environmental factors.

Therefore, the environmental factors controlling the occurrence of obesity are the key to treatment.

Doctors accustomed to taking medications need to recognize diet and behavioral therapy as the cornerstone of obesity treatment.

銆€銆€Scientific food composition and individualized absorption become the key to dietary control.

Correcting the extra energy expenditure of unhealthy lifestyles and proper exercise can improve preventive resistance, and is the main cause of complications associated with excessive disease.

銆€銆€On the basis of diet and behavioral therapy, if the patient’s body mass index 鈮?24kg / m2, accompanied by complications such as hyperglycemia, hypertension, hyperlipidemia, weight-bearing arthritis or sleep apnea syndrome, consider addingWeight loss drugs.

銆€銆€The patient’s body mass index 鈮?28kg / m2, after 3?
After 6 months of simple diet control and behavioral therapy, the target of 5% weight loss cannot be achieved. Regardless of whether there is any complication, weight loss medication can be considered.

銆€銆€For people with severe obesity, diet, behavior and medication are still not effective in reducing weight and improving complications. Surgical treatment may be considered.

Surgical treatment includes gastrointestinal interventional procedures and laparoscopic bandages.

There may be fewer people with severe obesity in the Chinese population than in Western countries due to different races, so the clinical evidence for surgical treatment of obesity is still insufficient.

銆€銆€Because of these, there is still not enough evidence to prove that drug weight loss can bring more long-term positive effects, so it is still not recommended to use drugs to treat too many children and adolescents.

銆€銆€At present, there are two main types of weight-reducing drugs that have been widely used clinically: the first is to act on central nervous system drugs, mainly to reduce weight loss by suppressing appetite; the second is to act on metabolic pathways, by inhibiting food.The absorption reaches the goal of negative energy balance.

銆€銆€Acting on the central nervous system, suppressing the appetite of appetite drugs by the feeding center of the hypothalamic abdominal cavity and the feeding center of the hypothalamic area.

Changes in catecholamine neurotransmitters such as norepinephrine, dopamine, and serotonin in the above central nervous system pathway can cause changes in feeding behavior.

Central appetite suppressant drugs are used to stimulate appetite, reduce food intake and reduce body weight by stimulating the production of one or more of the above neurotransmitters, releasing or inhibiting their reuptake.

銆€銆€Amphetamine and its derivatives are the earliest and widely used central appetite suppressants, including bupropion, horseshoe, phentermine, fenfluramine, ephedrine, etc., which have been confirmed by clinical applications for decades.Weight loss.

Because of the potential addictiveness of drugs such as bupropion, and the subsequent effects of fenfluramine on heart valves and prone to pulmonary hypertension, it has withdrawn from the clinical practice in most European and American countries.

銆€銆€Sibutramine hydrochloride is safer and more tolerant and has been widely used.

It exerts a role in inhibiting norepinephrine, dopamine and serotonin re-substitution through secondary (M1) and primary (M2) amine metabolism, increasing satiety and accelerating energy expenditure, and does not release the above neurotransmitters.influences.

Common adverse reactions caused by the drug include headache, dizziness, dry mouth, mouth pain, constipation, palpitations, and insomnia.

The effects of different studies reported by sibutramine on blood pressure and heart rate are not the same.

However, patients with underlying cardiovascular disease are still not recommended to take sibutramine to lose weight.

銆€銆€In 2001, Peking Union Medical College Hospital led a pre-market clinical trial of sibutramine in six hospitals across the country. A total of 250 patients participated in a randomized, double-blind, placebo-controlled study.

After 24 weeks of treatment, the patient lost weight (6.

52卤3.

95) kg, and can significantly reduce fasting and 1 hour postprandial blood glucose.

銆€銆€Acts on the gastrointestinal tract, inhibits food absorption, digestive tract, pancreatic lipase inhibitor, orlistat, which can specifically bind irreversibly to the gastric pancreatic lipase triglyceride binding site, resulting in approximately 30% triglyceride in the diet.The ester is not decomposed and absorbed, and it is replenished with feces. At the same time, the decomposition of triglyceride produces glycerol, and the production of free fatty acid and monoglyceride is also reduced. Because of the presence of glycerol, the absorption of cholesterol promotes the absorption of cholesterol.The absorption of the small intestine is correspondingly reduced, which promotes the negative balance of energy and achieves the weight reduction effect.

銆€銆€The results of a 24-week treatment of more than 400 obese patients led by Peking Union Medical College Hospital showed that patients lost weight (6).

05卤0.
21) kg, and the patient’s blood pressure, blood lipids and blood sugar levels were significantly improved.

Less than 1% of the drugs absorbed into the blood after taking orlistat.
Drug-related adverse reactions mainly include metabolic tract symptoms such as fecal gastrointestinal tract exhaust, oily spots, stool urgency, fat stools and increased stool frequency.

Orlistal is not recommended for patients with gastrointestinal disorders, cholestasis or gastrointestinal surgery.

銆€銆€New and under-reported weight-reducing drugs have led to significant adverse reactions or limited therapeutic effects due to weight-reducing drugs that have driven the development of new drugs.

Among them, the endocannabinoid CB1 receptor antagonist of the central nervous system is a currently concerned weight-loss drug, which achieves an appetite suppressing effect by selectively replacing the central cannabinoid CB1 receptor.

At the same time, it can increase the expression of adiponectin gene from the transcriptional level in relative tissues, thereby exerting an alternative to weight loss effects on insulin resistance, blood lipids, blood pressure and blood sugar.

銆€銆€Rimonabant is an endogenous cannabinoid CB1 receptor antagonist of the central nervous system.

A large-scale population study confirms that rimonabant can alleviate these risk factors while effectively reducing weight.

The drug is currently available in countries such as Europe, and clinical research on obese people in Asia is still underway.

The available clinical data suggest that the use of this drug may have adverse reactions of the nervous system, including depression.

銆€銆€There are many other types of drugs that have potential for weight loss at different targets being developed.

The phytosterols and sterols present in natural plants are structurally similar to plasma and are capable of competitively inhibiting the absorption of plasma in the small intestine. The analogy of the analog (FM-VP4) in animal and human trials demonstrates that the diet does not change.In this case, it has the effect of reducing body weight and lowering plasma LDL plasma levels.

銆€銆€The vasoactive peptide adrenomedullin, which has anti-oxidative stress, is also expressed in a small number of tissues. As a member of a small number of cytokine families, it may be involved in the occurrence of obesity, and has become a new target for weight-loss drugs.

銆€銆€Octadecanase Coenzyme A desaturase is the rate-limiting enzyme in the biosynthesis of monosubstituted unsaturated fatty acids. It is an important metabolic point of metabolism. Fatty acid hydroxylase inhibitors can inhibit the activity of SCD and induce oxidative oxidation to reduce weight.Effect.
銆€銆€Basic research on fatty acid synthase inhibitors shows that the compound FAS-57, 183 can exert an appetite-suppressing effect through the central nervous system, while FAS-89B can stimulate the oxidative oxidation rate in the body, especially in light tissues, and the above compounds are sufficiently significant alone and in combination.The weight loss effect, and animal tests show good safety.

銆€銆€Tyrosine phosphorylation is an important signaling pathway for insulin and leptin. Protein tyrosine phosphatase 1B (protein tyrosine phosphatase 1B, PTP1B) has been shown to be an important negative regulator of insulin and leptin signaling, PTP1BInhibitors improve the effects of these two hormones by enhancing the signaling of insulin and leptin to achieve the goal of treating type 2 diabetes and obesity.

銆€銆€Mitochondria-dissolved hydroxy-catenin (UCP-1, 2, 3) and 尾3-adrenergic receptors are involved in the development of obesity by affecting the heat production of mild tissues, and are currently being studied as targets for reducing the effects of heavy drugs, with a view to discovering new ones.The increase in energy-consuming drugs reaches the goal of mobilizing assistant organizations to reduce weight.

銆€銆€In general, although the emerging new drugs provide clinicians with powerful therapeutic weapons, weight loss treatment still requires comprehensive treatment based on diet, exercise, and behavioral therapy, scientifically and rationally, and the treatment goal is to reduce the original5% of body weight?
10%, and try to be close to the ideal weight, maintain weight after weight loss, prevent and improve obesity-related complications.