Role Of Membrane Lipids in Developing Insulin resistant Diabetes Mellitus Type II in Caucasians and African Americans.

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Title: Role Of Membrane Lipids in Developing Insulin resistant Diabetes Mellitus Type II in Caucasians and African Americans.
Author: Allen, Hengameh G.
Advisors: Jonathan C. Allen, Chair
Brenda Alston-Mills, Member
Leon C. Boyd, Member
Gregory P. Fenner, Member
Jacquelyn W. McClelland, Member
Abstract: Insulin resistance in diabetes (DMII) can result from membrane lipid (PM) changes. Membrane lipids play a major role in hormonal signal transduction and in appropriate amounts of such molecules may lead to either decreased, or increased membrane fluidity. Therefore, in this study we determined whether PM differences exist between African Americans (BL) and Caucasians (W) and if differences contribute to impaired insulin binding (IB) in DMII. Methodology: Subjects were recruited from Caucasian Control (CC) (n=10), African American Control (AC) (n=10), Caucasian Diabetics (CD) (n=5), African American Diabetics (AD) (n=10) groups. The diabetics were type II diabetics on daily insulin injections (age and sex-matched in both racial groups). The evaluations consisted of: three day dietary record, serum total cholesterol (TC), triglyceride (TRG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), glucose (Glu), hemoglobin A1C (A1C), insulin (Ins) levels and RBC membrane lipid composition including, fatty acids, phospholipids (PL), cholesterol (CH) and RBC insulin binding (IB), RESULTS: Cholesterol intake did not show any correlations with any blood constituents, membrane lipids or membrane properties. The macronutrient intake did not show a significant correlation with blood lipid levels, membrane properties and the anthropometric measurements as expected. The triglyceride levels were higher in diabetics (P <0.01). The lipoprotein evaluation indicated significant differences in VLDL (P <0.01), LDL (P <0.05) and HDL (P <0.0001) levels between control and diabetic subjects. There were no racial differences seen among the four groups. Diabetics had higher CH and it correlated with Glu (r= 0.65, P<0.05) and IB (r= -0.61, P <0.05). The CH/PL revealed strong correlation between LDL (r=0.42, P <0.01) and HDL (r= -0.56, P <0.05). The PM trans fatty acid levels (TFA) were highest in AD (P <0.01), but no correlations with IB & Glu. The PM saturated/polyunsaturated ratio (S/P) was higher in diabetics (P <0.05) correlating with insulin level (r= 0.42, P <0.01) & IB (r= -0.45, P <0.05), but no correlations with serum lipids occurred. The PL analysis showed no significant group differences for phosphatidyl inositol (PI) levels; however, significant racial differences were observed in phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC). The W showed higher PE levels than BL and lower PC. The RBC rheological (PE/PS) properties (deformability) was lower in diabetics and AC than CC. The saturated nature of RBC [(SPH+PC)/(PE+PS)] was the lowest in CC (P< 0.056). The combination of increased S/P, and increased saturated nature, decreased PE/PS, increased CH/PL indicate decreased membrane fluidity and decreased RBC deformability, which might contribute to decreased IB in DMII. Differences in PE and PC levels between BL and W possibly indicate a racial difference in cause of insulin resistance. The racial differences in developing DMII need to be recognized so the therapeutic agents can target the exact problem in the metabolic pathway to correct the insulin resistance.
Date: 2000-12-01
Degree: PhD
Discipline: Nutrition

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