Leptin and incident type 2 diabetes: risk or protection?
OBJECTIVE
The aim of this study was to investigate the association of leptin levels with incident diabetes in middle-aged adults, taking into account factors purportedly related to leptin resistance.


METHODS
We conducted a case-cohort study (570 incident diabetes cases and 530 non-cases) representing the 9-year experience of 10,275 participants of the Atherosclerosis Risk in Communities Study. Plasma leptin was measured by direct sandwich ELISA.


RESULTS
In proportional hazards models adjusting for age, study centre, ethnicity and sex, high leptin levels (defined by sex-specific cut-off points) predicted an increased risk of diabetes, with a hazard ratio (HR) comparing the upper with the lower quartile of 3.9 (95% CI 2.6-5.6). However, after further adjusting additionally for obesity indices, fasting insulin, inflammation score, hypertension, triglycerides and adiponectin, high leptin predicted a lower diabetes risk (HR=0.40, 95% CI 0.23-0.67). Additional inclusion of fasting glucose attenuated this protective association (HR=0.59, 95% CI 0.32-1.08, p<0.03 for linear trend across quartiles). In similar models, protective associations were generally seen across subgroups of sex, race, nutritional status and smoking, though not among those with lower inflammation scores or impaired fasting glucose (interaction p=0.03 for both).


CONCLUSIONS
High leptin levels, probably reflecting leptin resistance, predict an increased risk of diabetes. Adjusting for factors purportedly related to leptin resistance unveils a protective association, independent of adiponectin and consistent with some of leptin's described protective effects against diabetes.
Schmidt
M I
MI
Graduate Studies Program in Epidemiology, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. mischmidt@orion.ufrgs.br
Duncan
B B
BB
Vigo
A
A
Pankow
J S
JS
Couper
D
D
Ballantyne
C M
CM
Hoogeveen
R C
RC
Heiss
G
G
D052242:Adiponectin / Q000097:blood; D001741:Black or African American / Q000706:statistics & numerical data; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D012307:Risk Factors; D012907:Smoking; D014280:Triglycerides / Q000097:blood; D014481:United States / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D014280:Triglycerides