Dataset Information

Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people.

ABSTRACT:

Background

Free fatty acids (FFAs) are associated with insulin secretion and insulin resistance. However, the associations among FFAs, obesity, and progression from a normal to a prediabetic state are unclear.

Methods

Nondiabetic subjects (5,952) were divided in two groups according to their body mass index (BMI): obese subjects (BMI ≥24 kg/m²) and nonobese subjects (BMI <24 kg/m²). Clinical and multiple glucolipid metabolism data were collected. The homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) was used. HbA1c level between 5.7% and 6.4% was considered prediabetic. Nonparametric tests, one-way ANOVA, and linear correlation analysis were performed. R and SPSS 23.0 software programs were used to analyze the results.

Results

A U-shaped relationship between FFAs and HOMA-IR was observed. After adjusting for potential confounders, the turning points of FFA levels in the curves were 0.54 mmol/L in the nonobese group and 0.61 mmol/L in the obese group. HOMA-IR levels decreased with increasing FFA concentrations before the turning points (regression coefficient [β]= - 0.9, P=0.0111, for the nonobese group; β=0.2, P=0.5094, for the obese group) and then increased (β=0.9, P=0.0069, for the nonobese group; β=1.5, P=0.0263 for the obese group) after the points. Additionally, our study also identified that FFAs were associated with the prediabetes status in obese individuals.

Conclusion

FFA levels were associated with insulin resistance in nondiabetic subjects, and HOMA-IR in nonobese individuals was more sensitive to FFA changes. Monitoring and controlling plasma FFA levels in obese subjects is significant in decreasing insulin resistance and preventing diabetes.

SUBMITTER: Xin Y

PROVIDER: S-EPMC6342222 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people.

Xin Yanlu Y Wang Yunyang Y Chi Jingwei J Zhu Xvhua X Zhao Hui H Zhao Shihua S Wang Yangang Y

Diabetes, metabolic syndrome and obesity : targets and therapy 20190117

<h4>Background</h4>Free fatty acids (FFAs) are associated with insulin secretion and insulin resistance. However, the associations among FFAs, obesity, and progression from a normal to a prediabetic state are unclear.<h4>Methods</h4>Nondiabetic subjects (5,952) were divided in two groups according to their body mass index (BMI): obese subjects (BMI ≥24 kg/m<sup>2</sup>) and nonobese subjects (BMI <24 kg/m<sup>2</sup>). Clinical and multiple glucolipid metabolism data were collected. The homeosta ...[more]

PMID: 30705599

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Project description:BackgroundInsulin resistance heightens the risk for type 2 diabetes mellitus and cardiovascular disease. Amelioration of insulin resistance may reduce this risk. The thiazolidinedone class of insulin sensitizers improves insulin action in individuals with insulin-resistant diabetes and nondiabetic individuals. However, there are few reports on the time of onset of such effects independent of reversal of glucotoxicity.ObjectiveThe goal of our study was to test whether the thiazolidinedione pioglitazone has prominent early metabolic effects that can be detected in an obese, nondiabetic, insulin-resistant population.MethodsWe conducted a randomized, double-blind, placebo-controlled, parallel-group trial in men with nondiabetic insulin resistance using a hyperinsulinemic euglycemic clamp technique (at low and high doses of insulin at 10 and 40 mU/m(2)/min, respectively). The patients were given 30 mg daily oral pioglitazone or placebo for 28 days. Patients underwent a baseline clamp before initiation of treatment, and again at 14 and 28 days of treatment.ResultsCompared with placebo, under high-dose hyperinsulinemia, pioglitazone led to significant increases in glucose disposal rates (GDR) of 1.29 mg/kg/min (90% CI, 0.43-2.15; 39%; P=0.008) that were detectable at 2 weeks of treatment and persisted at 4 weeks of treatment. Under low-dose hyperinsulinemia, significant increases in GDR of 0.40 mg/kg/min (90% CI, 0.17-0.62; 95%; P=0.003) were observed at 4 weeks of treatment. These responses were accompanied by robust suppression of free fatty acids under hyperinsulinemic conditions, and by significant increases in circulating basal total adiponectin at 2 and 4 weeks of treatment.ConclusionsSignificant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712.

Project description:BACKGROUNDPostreceptor insulin resistance (IR) is associated with hyperglycemia and hepatic steatosis. However, receptor-level IR (e.g., insulin receptor pathogenic variants, INSR) causes hyperglycemia without steatosis. We examined 4 pathologic conditions of IR in humans to examine pathways controlling lipid metabolism and gluconeogenesis.METHODSCross-sectional study of severe receptor IR (INSR, n = 7) versus postreceptor IR that was severe (lipodystrophy, n = 14), moderate (type 2 diabetes, n = 9), or mild (obesity, n = 8). Lipolysis (glycerol turnover), hepatic glucose production (HGP), gluconeogenesis (deuterium incorporation from body water into glucose), hepatic triglyceride (magnetic resonance spectroscopy), and hepatic fat oxidation (plasma β-hydroxybutyrate) were measured.RESULTSLipolysis was 2- to 3-fold higher in INSR versus all other groups, and HGP was 2-fold higher in INSR and lipodystrophy versus type 2 diabetes and obesity (P < 0.001), suggesting severe adipose and hepatic IR. INSR subjects had a higher contribution of gluconeogenesis to HGP, approximately 77%, versus 52% to 59% in other groups (P = 0.0001). Despite high lipolysis, INSR subjects had low hepatic triglycerides (0.5% [interquartile range 0.1%-0.5%]), in contrast to lipodystrophy (10.6% [interquartile range 2.8%-17.1%], P < 0.0001). β-hydroxybutyrate was 2- to 7-fold higher in INSR versus all other groups (P < 0.0001), consistent with higher hepatic fat oxidation.CONCLUSIONThese data support a key pathogenic role of adipose tissue IR to increase glycerol and FFA availability to the liver in both receptor and postreceptor IR. However, the fate of FFA diverges in these populations. In receptor-level IR, FFA oxidation drives gluconeogenesis rather than being reesterified to triglyceride. In contrast, in postreceptor IR, FFA contributes to both gluconeogenesis and hepatic steatosis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778556, NCT00001987, and NCT02457897.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases, US Department of Agriculture/Agricultural Research Service 58-3092-5-001.

Dataset Information

Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people.

Background

Methods

Results

Conclusion

Publications

Elevated free fatty acid level is associated with insulin-resistant state in nondiabetic Chinese people.

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