This article is more than 5 years old. Information may no longer be current.
Changes in metabolic risk factors, biochemical markers observed years before type 2 diabetes onset
Click Here to Manage Email Alerts
In initially healthy men and women who went on to develop type 2 diabetes, researchers observed changes in several metabolic risk factors and biochemical markers up to 2 decades before disease diagnosis when compared with healthy controls, according to findings published in Nutrition & Diabetes.
“The comparison of long-term trajectories of risk factors between those who do and those who do not develop [type 2 diabetes] may help to identify at which time point these trajectories start to deviate before the development of overt disease,” Gerben Hulsegge, MSc, of the Centre for Nutrition, Prevention and Health Services at the National Institute for Public Health and the Environment in the Netherlands, and colleagues wrote. “Such insight into the timing and the extent of pathophysiological changes before symptoms occur may provide indications for the optimal timing of preventive actions. Trajectories of BMI and waist circumference are of particular importance since these are strong modifiable risk factors of [type 2 diabetes].”
Hulsegge and colleagues analyzed data from 6,217 adults without diabetes at baseline participating in at least two waves of the Doetinchem Cohort Study, a population-based, longitudinal study conducted in the Netherlands (2,913 men). Participants completed a clinical exam in wave 1 (1987-1991), wave 2 (1993-1997), wave 3 (1998-2002), wave 4 (2003-2007) and wave 5 (2008-2012); response rates were at least 75% for waves 2 to 5. Measurements included weight, height, waist circumference, diastolic and systolic blood pressure, total and HDL cholesterol and retrospectively examined triglycerides, alanine aminotransferase, gamma glutamyltransferase, high-sensitivity C-reactive protein, uric acid, cystatin C and creatinine levels; type 2 diabetes was self-reported. For each case of incident type 2 diabetes, six controls were randomly matched by age and sex and study wave. Researchers followed participants retrospectively for 6 to 21 years (mean, 10.6 years), depending on the wave in which type 2 diabetes was reported or control was matched. Researchers used generalized estimating equations to analyze trajectories preceding cases of incident diabetes.
Within the cohort, 194 men and 161 women developed type 2 diabetes; mean age at case ascertainment was 61 years for men and women.
Among participants with a 21-year follow-up period, those with type 2 diabetes had higher BMI, diastolic and systolic BP, total cholesterol and lower HDL cholesterol vs. cases at 20 years prior to case ascertainment, according to the researchers. Among the same participants, at 15 years prior to case ascertainment, levels of other metabolic risk factors and biochemical markers, including glucose, waist circumference, triglycerides, alanine aminotransferase, gamma glutamyltransferase, C-reactive protein and uric acid, were similar or higher than among controls.
Researchers observed that participants who developed incident type 2 diabetes had larger, unfavorable changes in the 15 to 20 years before diagnosis for BMI, HDL cholesterol and random glucose (P for interaction < .01). BMI, for example, increased by a mean 1.5 kg/m² and 2.2 kg/m² for men and women, respectively, between waves 1 through 5 when compared with controls, whose BMI remained stable over time (P > .05).
During the last 5 years before case ascertainment, between-group differences for metabolic risk factors and biochemical markers remained stable or decreased, except for glucose in men and women and C-reactive protein in men only, the researchers wrote.
“Since the diagnosis of [type 2 diabetes] occurred at an unknown time point during the 5 years preceding case ascertainment, medical treatment and lifestyle changes will have often already started before the wave in which a respondent reported a diagnosis of [type 2 diabetes],” the researchers wrote. “This implies that medical treatment and lifestyle intervention after the diagnosis of [type 2 diabetes] had a large, favorable impact on levels of almost all metabolic risk factors and biochemical markers.”
After adjusting for BMI, differences for all metabolic risk factors and biochemical markers were attenuated except for random glucose level; there were no between-sex differences.
“In general, the incidence of [type 2 diabetes] is relatively low before the age of 45 [years] and increases exponentially thereafter, with 90% of the incident [type 2 diabetes] cases being diagnosed after age 45 [years],” the researchers wrote. “Since the present study showed that the differences in trajectories of metabolic risk factors and biochemical markers between those with and without incident [type 2 diabetes] start to develop more than 15 to 20 years before diagnosis, this indicates that measures to prevent [type 2 diabetes] are already warranted before age 25 [years] and onwards.”
The researchers added that the findings suggest that it may be of interest to investigate whether repeated measurements of risk factors can improve risk prediction for development of type 2 diabetes. – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts