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▎WuXi AppTec content team editors Diabetes is usually divided into four categories: type 1, type 2, special types and gestational diabetes, of which type 2 is the most common
.
The prominent pathophysiology of type 2 diabetes is dysglycemia resulting from diminished insulin action, which is generally classified into two broad categories of causes: peripheral insulin resistance and/or insulin deficiency
.
With the attention to the heterogeneity of diabetes, more accurate diagnosis and treatment classification is also being explored
.
Previous studies have suggested that, in type 2 diabetes, the etiology of insulin deficiency includes increased insulin clearance and increased insulin degradation, in addition to the generally believed decrease in insulin secretion due to pancreatic β-cell degeneration
.
A study published in the NEJM Evidence recently explored this further by identifying a group of patients with type 2 diabetes whose pathophysiology was characterized by elevated insulin clearance, and analyzing this group of patients.
The clinical features found that they were generally not obese, had good beta-cell insulin secretion and even better insulin sensitivity, but had lower insulin levels and higher fasting blood glucose
.
The paper points out that if this new subtype is further validated, it may bring changes to the precision treatment of these patients
.
Screenshot source: NEJM Evidence This achievement comes from the Japanese diabetes medical team
.
Previously, the research team has reported a case of type 2 diabetes with decreased fasting blood insulin concentration and increased insulin clearance
.
The research team conducted an analysis of more patients, recruiting 101 newly diagnosed, untreated type 2 diabetes patients at the Jinnouchi Hospital Diabetes Clinic in Kumamoto, Japan (78.
2% male, average 54.
1 years)
.
These patients were selected considering that they usually do not have advanced, severe pancreatic beta-cell dysfunction
.
The researchers assessed the patients' insulin metabolic clearance rate (MCRI) by a hyperinsulinemic-euglycemic clamp test, and defined an elevated insulin clearance rate as MCRI > 700 ml/min/m2 with reference to previous study data
.
A total of 44 (44%) patients had elevated insulin clearance, and the median MCRI was significantly higher than the other patients (842 ml/min/m2 vs 570 ml/min/m2)
.
Patients with increased insulin clearance had some distinct clinical features compared to those with no increased insulin clearance: they were generally not obese (median body mass index [BMI] 22.
9 kg/kg), although there were no significant differences in age or sex.
m2 vs 27.
3 kg/m2); they had higher fasting blood glucose (median 178 mg/dl vs 146 mg/dl), lower fasting serum insulin levels (4.
2 mU/l vs 9.
6 mU/l), but higher glycated hemoglobin (HbA1c) levels were similar
.
They still had good insulin sensitivity, with a significantly higher median steady-state glucose infusion rate/steady-state insulin (103.
7 mg glucose⋅l/U/kg/min vs 45.
6 mg glucose⋅l/U/kg/min ) and lower HOMA-IR values (1.
85 vs 3.
9); pancreatic β-cell insulin secretion was also well preserved (daily urinary C-peptide excretion was similar, median 85.
6 μg/day vs 89.
6 μg/day)
.
There were no clinically significant differences in the duration of diabetes, percentage of family history of diabetes, diabetic retinopathy, and renal or liver function test results between the two groups
.
Based on blood glucose and insulin-related indicators, the research team speculated that hyperglycemia in these patients was caused by increased insulin clearance rather than insulin resistance
.
This is the exact opposite of what is common in European and American patients
.
Patients with type 2 diabetes in Europe and the US are more likely to have hyperinsulinemia (due to decreased insulin clearance and obesity-related decreased insulin sensitivity)
.
Image source: The 123RF paper further discusses that insulin clearance may be genetically regulated, and studies have reported higher hepatic insulin clearance in Japanese populations than in Caucasians and Mexicans
.
The insulin clearance process in the liver degrades more than half of the insulin secreted by pancreatic beta cells into the portal vein of the liver
.
In addition, despite studies suggesting that liver cell injury may impair hepatic clearance of insulin, nearly one-third of patients with elevated hepatic transaminases in this study had increased insulin clearance, suggesting that this may also occur in extrahepatic organs Increased insulin clearance
.
The research team also objectively raised the limitations of the study.
For example, this was a single-center study with a small sample size and did not assess insulin secretion
.
Overall, however, this study suggests that impaired insulin action due to increased insulin clearance is an important pathogenesis in this newly identified subtype of type 2 diabetes, and more studies are expected to confirm this in the future
.
.
The prominent pathophysiology of type 2 diabetes is dysglycemia resulting from diminished insulin action, which is generally classified into two broad categories of causes: peripheral insulin resistance and/or insulin deficiency
.
With the attention to the heterogeneity of diabetes, more accurate diagnosis and treatment classification is also being explored
.
Previous studies have suggested that, in type 2 diabetes, the etiology of insulin deficiency includes increased insulin clearance and increased insulin degradation, in addition to the generally believed decrease in insulin secretion due to pancreatic β-cell degeneration
.
A study published in the NEJM Evidence recently explored this further by identifying a group of patients with type 2 diabetes whose pathophysiology was characterized by elevated insulin clearance, and analyzing this group of patients.
The clinical features found that they were generally not obese, had good beta-cell insulin secretion and even better insulin sensitivity, but had lower insulin levels and higher fasting blood glucose
.
The paper points out that if this new subtype is further validated, it may bring changes to the precision treatment of these patients
.
Screenshot source: NEJM Evidence This achievement comes from the Japanese diabetes medical team
.
Previously, the research team has reported a case of type 2 diabetes with decreased fasting blood insulin concentration and increased insulin clearance
.
The research team conducted an analysis of more patients, recruiting 101 newly diagnosed, untreated type 2 diabetes patients at the Jinnouchi Hospital Diabetes Clinic in Kumamoto, Japan (78.
2% male, average 54.
1 years)
.
These patients were selected considering that they usually do not have advanced, severe pancreatic beta-cell dysfunction
.
The researchers assessed the patients' insulin metabolic clearance rate (MCRI) by a hyperinsulinemic-euglycemic clamp test, and defined an elevated insulin clearance rate as MCRI > 700 ml/min/m2 with reference to previous study data
.
A total of 44 (44%) patients had elevated insulin clearance, and the median MCRI was significantly higher than the other patients (842 ml/min/m2 vs 570 ml/min/m2)
.
Patients with increased insulin clearance had some distinct clinical features compared to those with no increased insulin clearance: they were generally not obese (median body mass index [BMI] 22.
9 kg/kg), although there were no significant differences in age or sex.
m2 vs 27.
3 kg/m2); they had higher fasting blood glucose (median 178 mg/dl vs 146 mg/dl), lower fasting serum insulin levels (4.
2 mU/l vs 9.
6 mU/l), but higher glycated hemoglobin (HbA1c) levels were similar
.
They still had good insulin sensitivity, with a significantly higher median steady-state glucose infusion rate/steady-state insulin (103.
7 mg glucose⋅l/U/kg/min vs 45.
6 mg glucose⋅l/U/kg/min ) and lower HOMA-IR values (1.
85 vs 3.
9); pancreatic β-cell insulin secretion was also well preserved (daily urinary C-peptide excretion was similar, median 85.
6 μg/day vs 89.
6 μg/day)
.
There were no clinically significant differences in the duration of diabetes, percentage of family history of diabetes, diabetic retinopathy, and renal or liver function test results between the two groups
.
Based on blood glucose and insulin-related indicators, the research team speculated that hyperglycemia in these patients was caused by increased insulin clearance rather than insulin resistance
.
This is the exact opposite of what is common in European and American patients
.
Patients with type 2 diabetes in Europe and the US are more likely to have hyperinsulinemia (due to decreased insulin clearance and obesity-related decreased insulin sensitivity)
.
Image source: The 123RF paper further discusses that insulin clearance may be genetically regulated, and studies have reported higher hepatic insulin clearance in Japanese populations than in Caucasians and Mexicans
.
The insulin clearance process in the liver degrades more than half of the insulin secreted by pancreatic beta cells into the portal vein of the liver
.
In addition, despite studies suggesting that liver cell injury may impair hepatic clearance of insulin, nearly one-third of patients with elevated hepatic transaminases in this study had increased insulin clearance, suggesting that this may also occur in extrahepatic organs Increased insulin clearance
.
The research team also objectively raised the limitations of the study.
For example, this was a single-center study with a small sample size and did not assess insulin secretion
.
Overall, however, this study suggests that impaired insulin action due to increased insulin clearance is an important pathogenesis in this newly identified subtype of type 2 diabetes, and more studies are expected to confirm this in the future
.
