Liver‐Fat Accumulation and Insulin Resistance in Obese Women with Previous Gestational Diabetes

Tiikkainen, Mirja; Tamminen, Marjo; Häkkinen, Anna‐Maija; Bergholm, Robert; Vehkavaara, Satu; Halavaara, Juha; Teramo, Kari; Rissanen, Aila; Yki‐Järvinen, Hannele

doi:10.1038/oby.2002.118

Cited by 141 publications

(128 citation statements)

References 73 publications

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“…Specifically, our findings indicate that ectopic fat in the liver may be related to visceral fat stores. This relationship between liver lipid and visceral adiposity has been noted in some (34,38) but not all (29,30) studies. Most interestingly, we observed that liver lipid infiltration tended to be greater in overweight individuals who had enlarged adipocytes and increased visceral abdominal adiposity.…”

Section: Response To Interventionmentioning

confidence: 95%

Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, β-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects

Larson‐Meyer

Heilbronn²,

Redman³

et al. 2006

Diabetes Care

442

338

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THE PENNINGTON CALERIE TEAMOBJECTIVE -The purpose of this article was to determine the relationships among total body fat, visceral adipose tissue (VAT), fat cell size (FCS), ectopic fat deposition in liver (intrahepatic lipid [IHL]) and muscle (intramyocellular lipid [IMCL]), and insulin sensitivity index (S i ) in healthy overweight, glucose-tolerant subjects and the effects of calorie restriction by diet alone or in conjunction with exercise on these variables. RESEARCH DESIGN AND METHODS-Forty-eight overweight volunteers were randomly assigned to four groups: control (100% of energy requirements), 25% calorie restriction (CR), 12.5% calorie restriction ϩ12.5% energy expenditure through structured exercise (CREX), or 15% weight loss by a low-calorie diet followed by weight maintenance for 6 months (LCD). Weight, percent body fat, VAT, IMCL, IHL, FCS, and S i were assessed at baseline and month 6. RESULTS -At baseline, FCS was related to VAT and IHL (P Ͻ 0.05) but not to IMCL. FCS was also the strongest determinant of S i (P Ͻ 0.01). Weight loss at month 6 was 1 Ϯ 1% (control, mean Ϯ SE), 10 Ϯ 1% (CR), 10 Ϯ 1% (CREX), and 14 Ϯ 1% (LCD). VAT, FCS, percent body fat, and IHL were reduced in the three intervention groups (P Ͻ 0.01), but IMCL was unchanged. S i was increased at month 6 (P ϭ 0.05) in the CREX (37 Ϯ 18%) and LCD (70 Ϯ 34%) groups (P Ͻ 0.05) and tended to increase in the CR group (40 Ϯ 20%, P ϭ 0.08). Together the improvements in S i were related to loss in weight, fat mass, and VAT, but not IHL, IMCL, or FCS.CONCLUSIONS -Large adipocytes lead to lipid deposition in visceral and hepatic tissues, promoting insulin resistance. Calorie restriction by diet alone or with exercise reverses this trend.

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Section: Response To Interventionmentioning

confidence: 95%

Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, β-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects

Larson‐Meyer

Heilbronn²,

Redman³

et al. 2006

Diabetes Care

442

338

View full text Add to dashboard Cite

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“…24 A diminished entrapment capacity of adipose tissue leads to increased lipid fluxes in the circulation leading to ectopic fat storage in liver, skeletal muscle and pancreas, leading to insulin resistance and beta cell dysfunction. [25][26][27][28][29] In humans, larger leg fat mass by dual-energy X-ray absorptiometry or larger thigh fat area by computed tomography has been found to be associated with favourable levels of cardiovascular risk factors including lipids and glucose levels in a few studies now. [30][31][32][33][34][35] In line with the latter mechanism, the strongest negative associations of the hip circumference would be expected to be observed with triglycerides, which we found in the present study, followed by slightly weaker but relevant associations with glucose levels.…”

Section: Discussionmentioning

confidence: 99%

Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study

et al. 2004

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OBJECTIVE: Fat distribution as measured by waist-to-hip ratio has been shown to be an important independent predictor of glucose intolerance. Few studies, however, have considered the contributions of the waist and hip circumferences independently. The aim of this study was to investigate the independent associations of waist and hip circumference with diabetes in a large population-based study, and to investigate whether they also apply to other major components of the metabolic syndrome (hypertension and dyslipidemia). In addition, as previous studies were performed in older persons, we investigated whether these associations were present across adult age groups. METHODS: Weight, height, waist and hip circumferences were measured in 11 247 participants of the nationally representative Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. HDL-cholesterol, triglycerides, fasting and 2-h postload glucose were determined, and diastolic and systolic blood pressure was measured. After exclusion of persons already known to have diabetes, hypertension or dyslipidemia, logistic and linear regression were used to study cross-sectional associations of anthropometric variables with newly diagnosed diabetes, hypertension and dyslipidemia, and with continuous metabolic measures, all separately for men (n ¼ 3818) and women (n ¼ 4582). Analyses were repeated in the same population stratified for age. RESULTS: After adjustment for age, body mass index and waist, a larger hip circumference was associated with a lower prevalence of undiagnosed diabetes (odds ratio (OR) per one s.d. increase in hip circumference 0.55 (95% CI 0.41-0.73) in men and 0.42 (0.27-0.65) in women) and undiagnosed dyslipidemia (OR 0.58 (0.50-0.67) in men and 0.37 (0.30-0.45) in women). Associations with undiagnosed hypertension were weaker (OR 0.80 (0.69-0.93) in men and 0.88 (0.70-1.11) in women). As expected, larger waist circumference was associated with higher prevalence of these conditions. Similar associations were found using continuous metabolic variables as outcomes in linear regression analyses. Height partly explained the negative associations with hip circumference. When these analyses were performed stratified for age, associations became weaker or disappeared in the oldest age groups (age Z75 y in particular), except for HDL-cholesterol. CONCLUSION: We found independent and opposite associations of waist and hip circumference with diabetes, dyslipidemia and less strongly with hypertension in a large population-based survey. These results emphasize that waist and hip circumference are important predictors for the metabolic syndrome and should both be considered in epidemiological studies. The associations were consistent in all age groups, except in age Z75 y. Further research should be aimed at verifying hypotheses explaining the 'protective' effect of larger hips.

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“…Intramyocellular and intrahepatic lipids were found to be important determinants of insulin resistance in humans [16][17][18]. Adiponectin was shown to increase lipid oxidation in these tissues in animals and in vitro.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat

et al. 2005

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Aims/hypothesis: The adipokine adiponectin has insulin-sensitising, anti-atherogenic and anti-inflammatory properties. Recently, the genes for mouse and human adiponectin receptor-1 (ADIPOR1) and -2 (ADIPOR2) have been cloned. The aim of this study was to investigate whether genetic variants of the genes encoding ADIPOR1 and ADIPOR2 play a role in human metabolism. Materials and methods: We screened ADIPOR1 and ADIPOR2 for polymorphisms and determined their association with glucose metabolism, lipid metabolism, an atherogenic lipid profile and inflammatory markers in 502 non-diabetic subjects. A subgroup participated in a longitudinal study; these subjects received diet counselling and increased their physical activity. Results: We identified six variants of ADIPOR1 and seven variants of ADIPOR2. A single-nucleotide polymorphism (SNP) in the putative promoter region 8503 bp upstream of the translational start codon (−8503 G/A) of ADIPOR1 (frequency of allele A=0.31) was in almost complete linkage disequilibrium with another SNP (−1927 T/C) in intron 1. Subjects carrying the −8503 A and −1927 C alleles had lower insulin sensitivity, as estimated from a 75 g OGTT (p=0.04) and determined during a euglycaemic clamp (n=295, p=0.04); they also had higher HbA 1 c levels (p=0.02) and, although the difference was not statistically significant, higher liver fat (n=85, determined by proton magnetic resonance spectroscopy, p=0.056) (all p values are adjusted for age, sex and percentage of body fat). In the longitudinal study (n=45), the −8503 A and −1927 C alleles were associated with lower insulin sensitivity (p=0.03) and higher liver fat (p=0.02) at follow-up compared with the −8503 G and −1927 T alleles, independently of basal measurements, sex and baseline and follow-up percentage of body fat. Conclusions/interpretation: The present findings suggest that the −8503 G/A SNP in the promoter or the −1927 T/C SNP in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans.

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Liver‐Fat Accumulation and Insulin Resistance in Obese Women with Previous Gestational Diabetes

Cited by 141 publications

References 73 publications

Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, β-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects

Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, β-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects

Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study

Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat

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