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In the 1940s, Dr. Joslin from the United States introduced the concept that hyperglycemia is a primary factor in vascular complications associated with diabetes, suggesting that rigorous blood glucose management could avert the development and progression of these complications. At that time, this notion faced skepticism and sparked discussions regarding the potential of achieving near-normal blood glucose levels to prevent diabetic complications.

The UK Prospective Diabetes Study (UKPDS) initiated in 1977 and the Diabetes Control and Complications Trial (DCCT) launched in 1983 were pivotal in diabetes research, addressing the crucial question of whether intensive glucose-lowering interventions could mitigate the risk of complications in diabetic patients. The UKPDS findings indicated that a 0.9% reduction in HbA1c within the intensive treatment cohort compared to the standard treatment group led to significant outcomes: a 16% decrease in myocardial infarction, a 25% reduction in microangiopathy, a 21% decline in fundopathy, and a 33% drop in microalbuminuria. Similarly, the DCCT revealed that maintaining normal blood glucose levels could prevent or postpone the onset of microvascular complications in individuals with type 1 diabetes, resulting in a remarkable 76% reduction in the risk of early ophthalmological, renal, and neurological issues.

The 2008 Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) revealed that intensive glucose-lowering therapy was associated with increased mortality rates and did not lead to a significant reduction in cardiovascular risk among patients. This finding challenges the previously held belief that such therapy is beneficial for managing complications. Further investigations, including the ADVANCE study on macrovascular and microvascular events in type 2 diabetes patients and the US Veterans Diabetes Study (VADT), have also failed to establish a clear link between glucose-lowering therapy and cardiovascular advantages. The VADT's inability to demonstrate even microvascular benefits raises questions about the efficacy of aggressive glucose-lowering strategies.

On a positive note, a follow-up report a decade after the UKPDS indicated that, despite an increase in glucose levels among patients in the intensive treatment group, there was still a notable decrease in all diabetes-related outcomes, including heart attack risk. This finding alleviates concerns regarding glucose-lowering therapy. It is now understood that the effectiveness of intensive glucose-lowering therapy depends on selecting appropriate candidates, such as those with milder forms of diabetes, as seen in the UKPDS study. In contrast, older patients with more severe diabetes may experience a higher risk of severe hypoglycemia and weight gain from aggressive treatment.

This also suggests from a different perspective that initiating intensive glucose-lowering therapy earlier in the course of diabetes yields more favorable outcomes. Thus, the principle of managing blood glucose levels to avert diabetic complications remains valid; however, it should not be interpreted as "the lower the blood glucose, the better," contingent upon patient tolerance. The focus of blood glucose management is shifting from a group-based approach to a more individualized strategy, marking a new era in personalized diabetes treatment.

Diabetes has been acknowledged by human society for over 3,000 years, and if we consider the advent of insulin, effective diabetes treatment has been available for just over 90 years. Nonetheless, both the landscape of diabetes medications and the overarching treatment philosophies have experienced significant transformations.