Association of liver fat content with insulin resistance and islet p cell function in individuals with various statuses of glucose metabolism

Objective To study the association of liver fat content (LFC) with insulin resistance and β cell function. Methods One hundred and nine subjects including 31 cases with impaired glucose regulation (IGR), 31 newly diagnosed type 2 diabetes (NT2DM) and 47 normal controls (NC) with normal metabolic parameters were involved in the study. LFC was measured by 1H magnetic resonance spectroscopy (1H MRS) and the insulin resistance and β cell function were evaluated by oral 75 g glucose tolerance test. Results (1 ) LFCs were3.83% (2.35% ～7.59% ) ,12. 82% (8.10%～21.37%), and 21.99% (11.89%～34.43%), being progressively raised in the respective NC, IGR, NT2DM groups(P<0.01). (2) The subjects were divided into four subgroups according to LFC Quartile: Quartile 1 (LFC<4. 04% ) , Quartile 2(4. 04% ≤LFC<9. 77% ), Quartile 3 (9.77% ≤LFC<20.78% ) ,and Quartile 4( LFC≥20.78% ). Homeostasis model assessment of insulin resistance index (HOMA-IR) values were elevated significantly and progressively starting from Quartile 2(P<0. 01). (3) Insulin from 0 to 30 min ( △I30), the ratio of insulin from 0 to 30 min to glucose from 0 to 30 min ( △I30/ △G30) , C peptide from 0 to 30 min (△CP30) had a trend of increase in Quartile 2,then trended to decrease in Quartile 3. In Quartile 4, △CP30 and △I30/△G30 sharply decreased (P<0.05 or P<0.01). The ratio of C peptide from 0 to 30 min to glucose from 0 to 30 min ( △CP30/△G30) began to decrease from Quartile 3 (P<0. 05). The ratio of area under curve of C peptide to area under curve of glucose (CPAUC/GAUC) was significantly decreased from Quartile 3(P<0.05). From Quartile 3,glucose level became abnormally elevated to impaired fasting glucose and impaired glucose tolerance (P<0.01). (4) LFC was positively correlated with HOMA-IR (rs =0. 618 ,P<0.01), but was negatively correlated with △CP30(rs =-0.282), △CP30/△G30(rs = -0. 404), and CPAUC/GAUC(rs = -0. 308,all P<0.01). (5) Stepwise regression analysis demonstrated that LFC was the strongest predictor of HOMA-IR. Conclusions When LFC accumulated to 4% , insulin resistance occurred and the early phase of insulin secretion was compensatively increased. As the LFC further accumulated to 10% , both the early phase as well as β cell function in whole were deteriorated, and hyperglycemia developed. Key words: Impaired glucose regulation;  Diabetes;  Magnetic resonance spectroscopy;  Insulin resistance;  β cell function