Although a description of the disease now known as type 2 diabetes has existed for millennia, it is only in recent decades, thanks to the scientific method, that we have gained a better understanding of the mechanisms behind its development, progression, and consequences. There are hundreds of scientific studies on this topic. In this article, I summarize some of the most important studies that have influenced the therapeutic approach and management of type 2 diabetes, hoping that this will help you better understand the basis of the decisions regarding your condition.
Key Findings from Large-Scale Studies
Here are two notable excerpts from a combined analysis of individual participant data from 19 countries. This meta-analysis included information such as age at diabetes diagnosis, cardiovascular disease, and mortality. The main findings are as follows:
Early-onset diabetes significantly increases the risk of premature death:
"Overall, each decade of earlier diabetes diagnosis was associated with an approximately 3 to 4-year reduction in life expectancy. Our modeling suggested that, among individuals surviving to age 50, those diagnosed with diabetes at 30 years old died 14 years earlier than non-diabetics, those diagnosed at 40 years old died 10 years earlier, and those diagnosed at 50 years old died 6 years earlier."
Strict and early blood sugar control effectively prevents diabetes complications:
"Furthermore, we observed a substantial attenuation of diabetes-associated excess mortality after adjusting for glycemic markers, suggesting that early diabetes detection through screening and intensive glycemic management are relevant for preventing long-term complications in adults with type 2 diabetes."
The Diagnostic Threshold
The diagnosis of type 2 diabetes is primarily based on measuring blood sugar levels (glycemia). This can be done directly through a fasting blood test or after drinking a solution containing 75 grams of glucose. The results reflect the amount of glucose per unit of blood volume, expressed in mmol/L or mg/dL.
Alternatively, an indirect measurement can be obtained using glycated hemoglobin (HbA1c), which reflects the average blood sugar levels over the past two to three months. This value is expressed as a percentage.
Below are the diagnostic thresholds for type 2 diabetes and prediabetes, based on the 2018 Canadian clinical practice guidelines (1):
Beyond mere numbers, these values often represent life-changing events for individuals receiving a diagnosis. But where does the scientific evidence supporting these diagnostic thresholds come from?
The practice guidelines reference, among other sources, a key study published in Diabetes Care in November 2011 (2).
Study Design and Methodology
This study laid the foundation for many subsequent studies determining the threshold at which blood sugar levels are high enough to require medical intervention. The main benchmark used to establish this threshold was diabetic retinopathy, a diabetes-related eye disease.
What is Diabetic Retinopathy?
Diabetic retinopathy is a condition affecting the retina, the light-sensitive membrane at the back of the eye. It occurs when small blood vessels in the retina are damaged, often due to diabetes or hypertension. This damage can lead to blurred vision, dark spots, or, in severe cases, blindness. In type 2 diabetes, retinopathy is often already present at the time of diagnosis. The severity of eye damage can be quantified through retinal imaging.
Study Objectives and Methods
The researchers aimed to revalidate the link between blood sugar levels and the development of diabetic retinopathy. Previous studies had already identified a relationship between retinopathy and diabetes, forming the basis of diagnostic criteria. However, these studies were limited by small sample sizes, reducing their statistical power.
To overcome this limitation, researchers conducted a comparative cross-sectional study using a large international database covering 5 countries and nearly 45,000 participants.
Study Design
Each participant had at least two data points recorded:
A retinal photograph
A blood glucose measurement (fasting glucose, HbA1c, or both)
Statistical analysis was conducted to evaluate:
The number of retinopathy cases associated with different blood sugar levels.
The accuracy of blood sugar measurements in predicting diabetic retinopathy.
Key Results
Among the 44,623 participants in the study:
16,381 were non-diabetic, based on diagnostic criteria.
28,242 were diabetic.
3,002 participants had diabetic retinopathy.
The data was divided into 20 equal groups, each representing a different range of blood sugar levels. Researchers calculated odds ratios, comparing each group to a control group (those with the lowest blood sugar levels).
The results showed:
Fasting blood glucose (FPG): Individuals with levels between 6.4 and 6.8 mmol/L were 2.5 times more likely to have diabetic retinopathy than those with levels between 1.7 and 4.4 mmol/L.
HbA1c: Individuals with levels between 6.3 and 6.7% were 4.5 times more likely to have diabetic retinopathy than those with levels between 3.1 and 4.5%.
Glucose tolerance test: Individuals with 9.8 to 10.6 mmol/L had a 10 times higher likelihood of having diabetic retinopathy than those with levels between 1.1 and 4.3 mmol/L.
Determining the Diabetes Threshold
To optimize the diagnostic threshold, researchers performed a sensitivity/specificity analysis to assess how well blood sugar measurements could accurately predict diabetic retinopathy. The results confirmed that blood sugar levels were reliable indicators of retinopathy risk.
Based on this data, the researchers established the most accurate diagnostic thresholds for diabetes:
Fasting blood glucose: ≥ 6.5 mmol/L
HbA1c: ≥ 6.5%
Glucose tolerance test: ≥ 11.1 mmol/L
These findings validated the existing HbA1c and glucose tolerance test thresholds while suggesting a lower fasting blood glucose threshold, currently classified as prediabetes.
Implications for Diabetes Diagnosis and Treatment
This epidemiological study established a clear correlation between diabetic retinopathy and elevated blood sugar levels. Since retinopathy is relatively easy to diagnose and is strongly linked to diabetes, it serves as a valuable marker for setting diagnostic thresholds.
Limitations of the Study
Most participants were already diabetic and receiving glucose-lowering medications, which may have artificially lowered the estimated diagnostic threshold.
The ideal diagnostic threshold for other diabetes complications (beyond retinopathy) remains unclear.
The Importance of Early Intervention
Without intervention, 5–10% of people with prediabetes develop type 2 diabetes annually, and nearly half progress to diabetes within 10 years. Moreover, even small increases in HbA1c are linked to significantly higher cardiovascular mortality:
Compared to a baseline of 4.27%, the risk of cardiovascular death increases by 34% at an HbA1c of 6% (prediabetes threshold) and by 58% at 7% (diabetes threshold) (3).
Given the significant benefits of early treatment, a proactive approach to diabetes management is still warranted.
References
1- Punthakee, Z., Goldenberg, R., & Katz, P. (2018). Définition, classification et diagnostic du diabète, du prédiabète et du syndrome métabolique. Canadian Journal of Diabetes, 42(Suppl. 1), S10-S15. https://doi.org/10.1016/j.jcjd.2017.10.003
2- Colagiuri S, Lee CM, Wong TY, et al. Glycemic thresholds for diabetes-specific retinopathy: Implications for diagnostic criteria for diabetes. Diabetes Care. 2011;34:145-150.
3- Santos-Oliveira, R., Purdy, C., Pereira da Silva, M., dos Anjos Carneiro-Leão, A. M., Machado, M., & Einarson, T. R. (2011). Haemoglobin A1c levels and subsequent cardiovascular disease in persons without diabetes: a meta-analysis of prospective cohorts. Diabetologia, 54(6), 1327-1334.