Association of serum proinsulin with hormone replacement therapy in nondiabetic older women: the Rancho Bernardo Study.
OBJECTIVE
One putative benefit of hormone replacement therapy (HRT) is a reduced risk of diabetes or reduced fasting glucose level. We report here the association of HRT with proinsulin, insulin, and fasting and postchallenge glucose levels in older adults.


METHODS
Current HRT use was validated and cross-sectionally compared with diabetes-related variables in 785 women without diabetes by history or glucose tolerance test.


RESULTS
Median age was 72 years (range 50-97); median value of fasting plasma glucose, postchallenge plasma glucose, and proinsulin was 5.08 mmol/l, 6.93 mmol/l, and 9.3 pmol/l, respectively. In age-adjusted comparisons, current HRT use was associated with significantly lower fasting plasma glucose and higher postchallenge plasma glucose compared with never/previous HRT use, as well as with lower LDL and higher HDL cholesterol and higher triglycerides. Fasting and postchallenge intact insulin did not differ by HRT group, but proinsulin was significantly lower in current HRT users than in previous and never HRT users. The significant association between proinsulin and HRT status persisted after adjustment for age, waist-to-hip ratio, pulse pressure, LDL-to-HDL cholesterol ratio, triglycerides, fasting and postchallenge glucose, and intact insulin.


CONCLUSIONS
Reduced fasting and increased 2-h glucose replicate findings in a randomized clinical trial. The proinsulin effect has not been previously reported. Decreased fasting glucose and proinsulin levels in current HRT use suggest a potential antidiabetes effect of HRT. Increased postchallenge glucose in HRT, however, suggests insulin resistance and would be expected to increase the risk of heart disease.
Kim
Dong-Jun
DJ
Department of FamilyPreventive Medicine, School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0607, USA. ebarrettconnor@ucsd.edu
Barrett-Connor
Elizabeth
E
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism*; D003430:Cross-Sectional Studies; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood*
D001786:Blood Glucose; D011384:Proinsulin