Effect of Paternal Diabetes on Pre-Diabetic Phenotypes in Adult Offspring

OBJECTIVE Paternal and maternal type 2 diabetes, exclusive of gestational diabetes, may influence risk factors in the offspring differently (through possible epigenetic effects of parental diabetes) and are difficult to identify without accurate dates of diagnosis. We aimed to examine a metabolic phenotype in three different groups of offspring to see distinct paternal versus maternal effects. RESEARCH DESIGN AND METHODS We examined body composition and insulin action (M) in nondiabetic subjects and insulin secretion tested via acute insulin response (AIR) in normal glucose-tolerant full-heritage Pima Indian adults categorized by disparate parental diabetes status: 1) offspring of fathers with early-onset diabetes (age <35 years) and nondiabetic mothers (ODF; n = 10), 2) offspring of mothers with early-onset diabetes (age <35 years), not exposed to diabetes in utero with nondiabetic fathers (OMED; n = 11), and 3) a control group of offspring of parents without diabetes until >50 years of age (CON; n = 15). RESULTS ODFs were leaner than CONs and OMEDs (percent of body fat [%BF]: least-squares means adjusted for age and sex [95% CI]: 27.3 [23.3-31.3] in ODFs vs. 35.4 [32.2-38.5] in CONs and 32.4 [28.8-36.1] in OMEDs, P = 0.04). ODFs were more insulin sensitive (had a higher M) than OMEDs or CONs, but not after adjustment for age, sex, and %BF. AIR adjusted for M, age, sex, and %BF was lower in ODFs versus CONs and OMEDs (P < 0.05). CONCLUSIONS Adult ODFs were leaner and had lower early insulin secretion, despite being equally insulin sensitive after adjustment for body fat compared to the other groups, indicating a paternal imprinted effect.