At the 2022 Annual Meeting of Endocrinology and Metabolism Physicians of the Chinese Medical Doctors Association, Professor Li Xia from the Second Xiangya Hospital of Central South University published a report titled "Type 1 Diabetes and Metabolic Syndrome", which reviewed recent research on type 1 diabetes and metabolic syndrome. related introduction.
Reasons for the increase in T1DM population
The incidence of type 1 diabetes (T1DM) is increasing year by year. It is generally considered to be a disease of adolescents. However, according to the latest data from Diabetologia, T1DM accounts for 6% of people aged 0-14 years old, 35% of people aged 15-39 years old, and 35% of people aged 40-64 years old. Accounting for 43%, people aged 65 and above account for 16%, which is somewhat different from daily experience. It should be noted that the data includes adolescents with onset and growth to adults, and T1DM patients in Asia account for about 30% of the total number. According to domestic survey data, the incidence of T1DM in my country is increasing year by year, with a current increase of 4%.
So which group of people does the increase in incidence mainly come from?
According to Diabetologia 2003 data, the increased incidence of T1DM is mostly seen in people carrying non-susceptible human leukocyte antigens (HLA). In other words, the increased incidence is not due to genetic evolution, but to environmental factors.
What specific environmental factors are there?
Professor Li Xia cited a 2018 study by Current Diabetes Reports, which mainly includes coxsackie virus infection, intestinal flora, vaccines, diet, milk protein, vitamin D and other causes. At the same time, this also brings up another question. The number of people with type 2 diabetes (T2DM) is gradually increasing. It is generally believed to be due to weight gain and lifestyle. So, is this also the reason for the increase in T1DM patients?
Professor Li Xia explained that some scholars have already conducted a meta-analysis on this, and the research results show that high birth weight (>4000g) is related to a high risk of T1DM. For every 1000g increase, the risk of T1DM increases by 7%. In other words, weight gain Can induce the occurrence of T1DM. This is also known as the accelerator doctrine.
T1DM and insulin resistance
In recent years, many studies have shown that the onset of T1DM is not a simple autoimmune disease, but the result of the interaction between autoimmunity and insulin resistance.
A significant proportion of T1DM patients have metabolic disorders related to insulin resistance. According to research results over the years, 9.5%-29.3% are overweight, 3.9%-14.6% are obese, 4.8%-20.8% have high blood pressure, and 6.1%-21.2% have high density liptein cholesterol (HDL-C). 5.6%-17.3% high triglyceride (TG), 3.2%-28.6% metabolic syndrome. Insulin resistance is closely associated with cardiovascular risk and death in T1DM.
Insulin resistance is also associated with microvascular complications. Data published by Diabetic Medicine in 2021 show that the stronger the insulin resistance, the higher the risk of macrovascular disease/diabetic retinopathy/diabetic nephropathy.
In recent years, studies have found that high glucose toxicity, weight gain and hyperinsulinemia caused by insulin treatment, which were not paid much attention in the past treatment, are themselves important inducing factors of T1DM. Therefore, many scholars treat patients with metabolic syndrome/insulin resistance as T1DM is called dual diabetes. Accordingly, in terms of treatment, not only insulin replacement is required for such patients, but also insulin resistance needs to be improved.
Hyperglycemia will cause a decrease in glucose utilization, so hyperglycemia is an important cause of insulin resistance in T1DM. Although insulin treatment relieves glucotoxicity and can significantly improve the level of insulin resistance, it can also lead to hyperinsulinemia. A 2019 study published in Diabetes concluded that insulin resistance in T1DM is closely related to hyperinsulinemia.
There are two reasons why insulin treatment can lead to insulin resistance. First, it can cause hyperinsulinemia. On the other hand, insulin treatment can lower blood sugar and lead to weight gain at the same time. The EDC study followed patients with type 1 diabetes for 18 years and found that the prevalence of obesity increased from 3.4% to 22.7% and the prevalence of overweight increased from 28.6% to 42%.
DCCT and EDIC studies published in Diabetes Care in 2017 and 2019 showed that higher insulin doses were closely associated with worsening trends in several traditional cardiovascular disease risk factors (such as BMI, pulse rate, triglycerides, blood pressure, and cholesterol). Related, further study results showed that CVD and all-cause mortality increased with increasing BMI.
Professor Li Xia's research team also conducted a cross-sectional study on T1DM, including a total of 600 patients older than 10 years old and with disease duration greater than 6 months. The study found that the proportion of T1DM combined with overweight, hypertension, dyslipidemia, and metabolic syndrome Up to 10%. Moreover, with the prolongation of the course of the disease, patients with a course of more than 10 years have a significantly increased risk of developing insulin resistance and metabolic syndrome.
Potential drug treatment for T1DM that could replace insulin
Professor Li Xia emphasized that how to use early stage treatment to control patients' insulin resistance is an issue we should pay attention to. Can we explore potential T1DM treatment drugs to replace insulin treatment, such as metformin, rosiglitazone, SGLT2i, commonly used T2DM drugs? GLP-1RA?
Data published in Criculation in 2018 showed that metformin can improve insulin resistance in patients with T1DM, thereby improving cardiovascular risk-related assessment indicators, such as arterial pulse wave velocity.
As for rosiglitazone, there were relevant studies as early as 2005 in Diabetes. The study found that in patients with T1DM, rosiglitazone combined with insulin treatment can improve glycemic control and blood pressure without increasing insulin requirements, while patients treated with insulin and placebo required an 11% increase in insulin dose to improve glycemic control. End of study , weight gain and hypoglycemia were similar in both groups.
In 2009, Diabetes Research and Clinical Practice study data showed that for adults with latent autoimmune diabetes (LADA), compared with sulfonylureas, rosiglitazone can better protect pancreatic islet function and improve insulin sensitivity.
The currently popular role of SGLT2i in T1DM was also reported in Scientific Reports in 2017. It can reduce glycated hemoglobin (HbA1c) by 0.4%, fasting blood sugar by 1.14mmol/L, weight by 2.68kg, and systolic blood pressure by 3.37mmHg. Basics Insulin decreased by 4.2 units. As for another hot spot, GLP-1RA, the Expert Opinion on Pharmacotherapy in 2018 also reported its role in T1DM, which can reduce HbA1c by 3.34, reduce body weight by 2kg, and reduce the total insulin dose by 22 units.
Professor Li Xia emphasized that in the past clinical practice, insulin resistance in type 1 diabetes was easily overlooked. With the progress of scientific research, the known perspectives and unknown issues of insulin resistance in type 1 diabetes have become clearer.
