From mechanism to practice, how can insulin therapy contribute to higher quality blood glucose management?

With the disclosure of more mechanistic and clinical practice studies, blood glucose management is moving towards efficiency, safety and simplicity
.
There is a lot of interest in
how to achieve better blood glucose management with existing means.

At the 2022 Basic Meal Summit held on October 29, Professor Gao Yan, Chairman of the Conference, Peking University First Hospital, Professor Yang Huazhang, Guangdong Provincial People's Hospital, Professor Li Guangwei of Fuwai Hospital of Chinese Academy of Medical Sciences, Professor Li Yanbing of the First Affiliated Hospital of Sun Yat-sen University, Professor Zeng Longyi of the Third Affiliated Hospital of Sun Yat-sen University, Professor Yang Huixia of Peking University First Hospital and many other experts in the field of endocrinology elaborated on the mechanism of blood glucose formation, insulin treatment strategies and the clinical value of blood glucose monitoring technology.
Let's go back to the conference and see what the highlights are
.

Insulin intensive therapy

Make the dream of diabetes relief a reality

When glycemic control is poor, short-term admission for glycaemic regulation
may be considered.
Studies ^[1] have pointed out that for hospitalized patients with type 2 diabetes mellitus with poor glycemic control treated with basal insulin once daily or premixed insulin twice daily, insulin aspart + detemir can be compared with human insulin plus neutral protamine zinc insulin (NPH) after 2 weeks of treatment.
Smoother blood sugar control and reduced blood sugar fluctuations (Figure 1).

Fig.
1 Insulin aspart + insulin detemir intensive therapy may be a more preferred choice

In addition to better blood sugar control, can early insulin intensive therapy in patients with type 2 diabetes restore β cell function and achieve diabetes remission? Studies ^[2^] have pointed out that 134 patients with newly diagnosed type 2 diabetes who were treated with an insulin pump (with insulin aspart) for 2 weeks had a one-year diabetes remission rate of 50%.
, a two-year response rate of 30%, and 10% of patients still have disease remission
at four years.

Previous studies have suggested that after receiving short-term intensive insulin therapy for newly diagnosed type 2 diabetes, some patients may have remission for up to 9~50 months (blood sugar can be maintained close to normal without any hypoglycemic drugs), and scholars believe that insulin intensive therapy has induced a "honeymoon period"
.
Diabetes mellitus is clinically characterized by a slow onset, an intense need for insulin, and some reversible
diseases.
β cell biology is characterized by slow renewal, limited regeneration, and various tests
.
Therefore, the honeymoon phase induced by intensive treatment of
newly diagnosed type 2 diabetes mellitus has a theoretical basis.
It is hoped that through more exploration, the induction honeymoon period will allow patients to return to a non-diabetic state and minimize the long-term risk of
cardiovascular disease.

How can new technologies help with higher quality blood sugar control?

Several studies have confirmed that the time within the target range (TIR) of continuous glucose monitoring is closely related to the risk of diabetic microvascular and macrovascular complications and mortality ^[3-].
^7], glucose below the target range (TBR) is strongly associated
with diabetes-related poor prognosis.
Thus, TIR, time above target range (TAR), and TBR should be included in glycaemic control targets for assessing glycemic management, and the TIR international consensus recommends that most patients with diabetes should have a > of 70 percent TIR and a < of 4 percent of TBR ^[8].
^]
。

Based on the important role of the above monitoring indicators, researchers have also conducted a number of studies to observe the improvement effect
of various treatment strategies on TIR and other indicators.
Lifestyle interventions, patient education, continuous glucose monitoring, and novel basal insulin analogues are thought to improve TIR, TAR, and TBR
.
For example, studies ^[9] suggest that insulin degludec can effectively control sugar to reach the target range, and TIR index is better than insulin glargine, and the results of this study are worthy of clinical reference (Figure 2).

。

Fig.
2 Insulin degludec is more effective than insulin glargine in sugar control

(*There is a significant difference)

Insulin optimization treatment strategies from the perspective of blood glucose formation mechanism

Under physiological conditions, the liver and multiple organs and systems work together to regulate blood sugar to maintain fasting
blood glucose (FPG) levels.
In normal individuals, basal (fasting) blood glucose levels depend on the degree of
liver glucose output.
In type 2 diabetes, abnormal hepatic glucose production is increased, combined with increased glucagon levels and increased liver sensitivity to them, increased gluconeogenesis substrates, and increased oxidation of free fatty acids, resulting in increased
FPG levels.

It can be seen that FPG is of great significance in the development of diabetes, which can prioritize the control of basal hyperglycemia, can effectively improve insulin resistance and islet β cell function ^[10], improve overall blood glucose levels throughout the day, and drive glycosylated hemoglobin ( HbA _1c) Attainment of standards
.
Chinese studies ^[11] suggest that patients with HbA1c when the FPG target is set to ≤6.
1 mmol/L The compliance rate was significantly higher than that of patients with an FPG set of ≤ 7.
0 mmol/L (46.
1% versus 37.
7%), comparable to the group of patients with an FPG set of ≤ 5.
6 mmol/L, and had a low risk of hypoglycemia, similar
to the risk of hypoglycemia in the group of patients with an FPG set of ≤ 7.
0 mmol/L.
It can be seen that it is more appropriate
to set the FPG target of ≤ 6.
1mmol/L.

To achieve this goal, appropriate therapeutic agents
should be selected.
Basal insulin inhibits hepatic glucose output by reducing hepatic glycogenolysis and gluconeogenesis, and controls FPG from the source of mechanism ^[12,13].

。 Take the new generation of basal insulin deglucose, for example, which mimics physiological secretion, has a longer half-life, and has lower glycemic variability ^[14-17].

。 Several different studies have suggested that compared with drugs such as sitagliptin and insulin glargine U100, patients in the insulin degludec group have better FPG improvement and are more likely to achieve the FPG target of 6.
1 mmol/L ≤ (Fig.
3) ^[18-].
^22], worthy of reference by clinicians
.

Fig.
3 The FPG of insulin degludec is better

Grasp the window of opportunity for maternal and child health,

Aggressive management of hyperglycaemia in pregnancy