Background:
Type 2 diabetes mellitus (DM) results from insulin resistance (IR), pancreatic β-cell dysfunction, or both. We hypothesized that risk factors could differ for DM preceded predominantly by IR, β-cell dysfunction, or both. This hypothesis is particularly important for older adults, in whom β-cell dysfunction may be relatively common.
Methods:
During 18 years of follow-up among 3,899 older adults free of DM (mean±sd age =73.0±5.8), we identified 274 incident DM cases by DM medication use, fasting glucose (≥126 mg/dL), or 2-hour post-challenge glucose (≥200 mg/dL), for whom homeostatic model assessments for IR (HOMA-IR) and β-cell function (HOMA-B) were assessed after baseline and before DM diagnosis. Using median cutoffs of the follow-up HOMA-IR and HOMA-B, we subclassified incident DM into DM preceded by IR only (n=112), β-cell dysfunction only (n=70), or both (n=77). Using multivariate competing-risk Cox models, we tested whether DM risk factors were differentially associated with risk of each DM subclass.
Results:
Elevated triglyceride levels (≥150 mg/dL) and impaired fasting glucose (100-125 mg/dL) were each positively associated with DM, irrespective of the DM subclass. Other DM risk factors of older age, overweight, obesity, low HDL cholesterol, and hypertension had substantially varying relationships with risk of different DM subclasses (p<0.001 for the variations). For example, overweight (BMI=25-29.9 kg/m2) and obesity (BMI≥30 kg/m2) were each positively associated with DM preceded by IR only (hazard ratio [95% CI]= 2.21 [1.25-3.92] and 5.02 [2.81-9.00], respectively), but with a significant inverse association with DM preceded by β-cell dysfunction only (0.61 [0.37-1.00] and 0.33 [0.14-0.80], respectively) (Figure).
Conclusions:
Among older adults, some DM risk factors differ substantially depending on HOMA-IR or HOMA-B subclassification. These findings support our hypothesis of heterogeneity in incident DM, especially among older adults.
Risk Factors for Type 2 Diabetes Mellitus Preceded by β-Cell Dysfunction, Insulin Resistance, or Both in Older Adults
