Inflammation, insulin resistance, and adiposity: a study of first-degree relatives of type 2 diabetic subjects.
OBJECTIVE
Inflammatory markers such as C-reactive protein (CRP) are associated with insulin resistance, adiposity, and type 2 diabetes. Whether inflammation causes insulin resistance or is an epiphenomenon of obesity remains unresolved. We aimed to determine whether first-degree relatives of type 2 diabetic subjects differ in insulin sensitivity from control subjects without a family history of diabetes, whether first-degree relatives of type 2 diabetic subjects and control subjects differ in CRP, adiponectin, and complement levels, and whether CRP is related to insulin sensitivity independently of adiposity.


METHODS
We studied 19 young normoglycemic nonobese first-degree relatives of type 2 diabetic subjects and 22 control subjects who were similar for age, sex, and BMI. Insulin sensitivity (glucose infusion rate [GIR]) was measured by the euglycemic-hyperinsulinemic clamp. Dual-energy X-ray absorptiometry determined total and abdominal adiposity. Magnetic resonance imaging measured abdominal adipose tissue volumes.


RESULTS
First-degree relatives of type 2 diabetic subjects had a 20% lower GIR than the control group (51.8 +/- 3.9 vs. 64.9 +/- 4.6 micromol x min(-1) x kg fat-free mass(-1), P = 0.04). However, first-degree relatives of subjects with type 2 diabetes and those without a family history of diabetes had normal and comparable levels of CRP, adiponectin, and complement proteins. When the cohort was examined as a whole, CRP was inversely related to GIR (r = -0.33, P = 0.04) and adiponectin (r = -0.34, P = 0.03) and positively related to adiposity (P < 0.04). However, CRP was not related to GIR independently of fat mass. In contrast to C3 (r = 0.41, P = 0.009) and factor B (r = 0.43, P = 0.005), CRP was unrelated to factor D.


CONCLUSIONS
The insulin-resistant state is not associated with changes in inflammatory markers or complement proteins in subjects at high risk of type 2 diabetes. Our study confirms a strong relationship between CRP and fat mass. Increasing adiposity and insulin resistance may interact to raise CRP levels.
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia.
Adamandia D
AD
Kriketos
Jerry R
JR
Greenfield
Phil W
PW
Peake
Stuart M
SM
Furler
Gareth S
GS
Denyer
John A
JA
Charlesworth
Lesley V
LV
Campbell
D052242:Adiponectin; D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D002097:C-Reactive Protein