‘Subtle’ metabolic derangement seen decades before diabetes diagnosis
medwireNews: Research shows that changes in markers of the metabolic syndrome and fatty liver disease are present more than 20 years before people receive a diagnosis of type 2 diabetes.
Although these markers were within the normal range at the study participants’ baseline examinations in 1985–1996, the “subtle” changes detected nevertheless predicted later diabetes.
Participants who later developed diabetes had a higher baseline BMI, on average, than those who did not, at 27.3 versus 24.6 kg/m2. They also had higher levels of glucose, triglycerides, and uric acid, as well as lower levels of apolipoprotein (apo) A-1.
This “most likely reflects a reduced insulin sensitivity,” say Håkan Malmström (Karolinska Institutet, Stockholm, Sweden) and study co-authors.
Notably, the differences between cases and controls (five per case) in BMI, triglycerides, uric acid, and apo A-1 remained stable between baseline and the time of diabetes diagnosis. “Hence successively increased insulin resistance is unlikely to explain the onset of [type 2 diabetes],” writes the team in Diabetes, Obesity and Metabolism.
During an average 20 years of follow-up, there were 28,244 new diabetes diagnoses among 296,439 study participants (47% women) who did not have diabetes at baseline, giving an average 20-year risk of 8.1%.
People with the lowest baseline metabolic risk, with BMI less than 25 kg/m2, fasting triglycerides below 124 mg/dL and fasting glucose below 81 mg/dL, had an estimated 20-year risk of just 2.2% and 1.3% for men and women, respectively, aged 40-49 years. But this increased to a corresponding 63.5% and 69.6% for those who were obese (BMI ≥30 kg/m2) and had triglyceride levels of at least 124 mg/dL and glucose between 100 and 125 mg/dL.
The researchers say that early signs of impaired metabolism have been reported in previous studies, but none looking back as far before diabetes diagnosis as theirs.
Their research “indicates that biomedical processes associated with increased insulin resistance are present in the development of [type 2 diabetes] very early and emphasizes the importance of early detection and initiation of preventive measures,” they write.
They also suggest that, although not the aim of their research, development of a risk stratification tool based on the identified factors could be useful, noting that “[t]he variables used to estimate and describe the long term risk in the present study were few and readily available, [but] still with a clear relevance for the long term risk of developing type 2 diabetes.”
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