Leptin concentrations are associated with higher proinsulin and insulin concentrations but a lower proinsulin/insulin ratio in non-diabetic subjects.
BACKGROUND
Leptin (the product of the human OB gene) is increased in obese individuals, suggesting resistance to its effect. However, there is considerable variability in leptin levels at each level of body mass index (BMI), suggesting that genetic and environmental factors may regulate leptin concentrations. Previous data have suggested that leptin levels are associated with insulin resistance and in a few reports with impaired insulin secretion. We examined whether non-diabetic subjects, with elevated specific insulin and proinsulin levels, had increased leptin levels.


METHODS
We used a radioimmunoassay (RIA) to measure serum leptin levels in 197 non-diabetic Mexican Americans and non-Hispanic whites from the San Antonio Heart Study. We also evaluated whether leptin levels were associated with impaired insulin secretion or increased beta cell stress, as evaluated by the fasting proinsulin/insulin ratio. (Higher fasting proinsulin/insulin ratios are thought to reflect impaired insulin secretion.)


RESULTS
Leptin levels were significantly correlated with fasting specific insulin (r=0.55, P<0.001) and proinsulin (r=0.57, P<0.001) and inversely with the proinsulin/insulin ratio (r= -0.154, P=0.035) after adjustment for age, gender, ethnicity and 2 h glucose. These associations were similar in men and women and in Mexican Americans and in non-Hispanic whites. After further adjustment for BMI and waist-to-hip ratio (WHR), leptin levels remained significantly correlated with specific insulin (r=0.31, P<0.001) and proinsulin (r=0.24, P<0.001) although the magnitude of the associations were considerably attenuated.


CONCLUSIONS
We conclude that specific insulin and proinsulin are positively related to leptin levels and that these associations are to some degree independent of obesity and body fat distribution. Thus, subjects with increased insulin levels may be relatively resistant to the effects of leptin. However, leptin levels are associated with a decrease in the fasting proinsulin/insulin ratio suggesting that leptin levels are not associated with an impairment in insulin secretion.
Department of Medicine, University of Texas Health Science Center at San Antonio, 78284-7873, USA.
S M
SM
Haffner
H
H
Miettinen
L
L
Mykkänen
M P
MP
Stern
D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001824:Body Constitution; D015992:Body Mass Index; D005215:Fasting; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D020738:Leptin; D016014:Linear Models; D008297:Male; D008800:Mexico / Q000208:ethnology; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood*; D011506:Proteins / Q000378:metabolism*; D012885:Skinfold Thickness; D013781:Texas; D044465:White People
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011506:Proteins; D011384:Proinsulin