Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.
BACKGROUND
Insulin therapy may influence cardiovascular disease (CVD) and lipid metabolism in type 2 diabetes (T2D). Exaggerated postprandial lipaemia (PPL) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress (OS) and endothelial dysfunction. We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty (17 M) T2D patients were studied (mean Hba1c 8.4%) at baseline, following 6 weeks of insulin lispro (0.2 Iu kg-1) and vitamin C 1-g daily. Eight-h lipid and glucose profiles were measured following a fatty meal. Endothelial function (flow-mediated vasodilatation: FMD) and OS were measured at fasting, 4 h and 8 h.


METHODS
Glucose, body mass index, and total and LDL cholesterol remained unchanged. FMD improved. Placebo group: fasting, 1.1 +/- 1.2 to 4.2 +/- 1.1% (P < 0.001); 4-h, 0.3 +/- 1.2 to 3.1 +/- 0.9% (P < 0.01); 8-h, 0.7 +/- 1.1 to 3.76 +/- 1.1% (P < 0.001). Vitamin C group: fasting, 0.9 +/- 1.1 to 6.1 +/- 1.3% (P < 0.001); 4-h, 0.7 +/- 1.5 to 4.9 +/- 2.1% (P < 0.001); 8-h, 0.8 +/- 0.9 to 5.8 +/- 0.6% (P < 0.01). Post-prandial lipaemia was attenuated: TG area-under-curve (mmol L-1 8 h-1), 52.6 +/- 11 to 39.1 +/- 12.5 (placebo group), P < 0.02; and 56.9 +/- 8 to 40.1 +/- 10.3 (vitamin C group), P < 0.02. Oxidative stress was reduced, with greater changes in the vitamin C group.


CONCLUSIONS
Insulin may thus exert vascular benefits in T2D, by modifying fasting and postprandial lipid metabolism resulting in reduced OS and improved EF. Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF.
Evans
M
M
Cardiovascular Sciences Research Group, Department of Medicine, University Hospital of Wales, Cardiff, Heath Park, UK. evans2@ntlworld.com
Anderson
R A
RA
Smith
J C
JC
Khan
N
N
Graham
J M
JM
Thomas
A W
AW
Morris
K
K
Deely
D
D
Frenneaux
M P
MP
Davies
J S
JS
Rees
A
A
D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D061268:Insulin Lispro; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D019518:Postprandial Period
D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D001205:Ascorbic Acid