Multiple factors linked to type 2 diabetes glycemic progression
medwireNews: Extremes of bodyweight and high glycated hemoglobin (HbA1c) levels were two of the factors linked to rapid glycemic progression in a study of more than 7000 Chinese people with type 2 diabetes.
“There is marked heterogeneity in the rate of progression to insulin requirement in patients with type 2 diabetes,” explain Ronald Ma (The Chinese University of Hong Kong, China) and colleagues.
“Whereas some patients can maintain optimal glycemic control with oral glucose-lowering drugs for prolonged periods, others experience rapid deterioration in glycemia, requiring early insulin treatment,” they add.
Bodyweight and HbA1c have previously been associated with glycemic progression, but predominantly in White populations, note the researchers. They therefore looked at clinical or genetic predictors in an Asian population using data from the Hong Kong Diabetes Register for insulin-naïve patients, aged 56.8 years on average, 47% of whom were men. The median duration of diabetes was 4 years.
Over a median follow-up of 8.8 years, 44% of the study population experienced glycemic progression. This was defined as the need for continuous insulin or by two consecutively high HbA1c measurements of 8.5% (69 mmol/mol) or more while taking at least two oral glucose-lowering drugs.
Patients with a BMI below 18.5 kg/m2 had a 66% increased risk for glycemic progression, compared with those with a BMI of 18.5–23.0 kg/m2, while people with a BMI above 25 kg/m2 had a 12% increased risk.
Taking an HbA1c of less than 7% (53 mmol/mol) as the reference, the researchers report double the risk for glycemic progression among patients with an HbA1c of 7% to 9% (53–75 mmol/mol), with a hazard ratio (HR) of 2.14, whereas the risk was quadrupled when HbA1c levels exceeded 9% (HR=4.07).
Ma and team found that being diagnosed before the age of 40 years was associated with a 28% increased risk for glycemic progression versus being diagnosed later. Triglyceride levels, tobacco use, and microvascular complications were also predictive in this population of patients, they report in PLOS Medicine.
A polygenic risk score (PRS) based on 123 known single nucleotide polymorphisms for type 2 diabetes was also associated with early age of diagnosis and rapid glycemic progression. This was validated in a replication study using data from the Hong Kong Diabetes Biobank.
“Our work highlights the potential utility of incorporating PRSs for drug response to guide clinical management of [type 2 diabetes],” Ma and team write.
A total of 2519 patients were started on insulin as a result of glycemic progression and the team notes that for 33.2% of these individuals there was a lag time of 1.3 years after treatment with oral glucose-lowering drugs had failed. This lag in insulin use “represents an important treatment gap in clinical practice,” they suggest.
There may be potential overlap between the pathogenesis of type 2 diabetes and glycemic progression, the researchers observe, noting that “the contributions of both modifiable and nonmodifiable risk factors enable the precise identification of high-risk individuals for close monitoring and early treatment intensification to maintain glycemic durability.”
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