Relationship Between Insulin Sensitivity and Plasma Leptin Concentration in Lean and Obese Men

Segal, Karen R.; Landt, Michael; Klein, Samuel

doi:10.2337/diab.45.7.988

Cited by 388 publications

(202 citation statements)

References 15 publications

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“…In nondiabetic, but not in type 2 diabetic subjects a strong relationship between leptin levels and insulin action on glucose uptake in subcutaneous fat cells was also found. Previous studies have shown a relationship between in vivo insulin resistance and leptin levels [28,29], and leptin has been shown to cause insulin resistance in rat fat cells in vitro [30]. Since leptin was associated with subcutaneous fat cell size as well as insulin resistance in vitro in this study, leptin may serve as a marker and possibly be a link between fat cell size and insulin resistance.…”

Section: Discussionsupporting

confidence: 59%

Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’

et al. 2007

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Aims/hypothesis The aim of this study was to explore whether fat cell size in human subcutaneous and omental adipose tissue is independently related to insulin action and adipokine levels. Materials and methods Fat cells were prepared from abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non-diabetic subjects and from omental biopsies obtained from 37 non-diabetic subjects. Cell size and insulin action on glucose uptake capacity in vitro were assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and adipokines and NEFA were measured. Results Negative correlations were found between subcutaneous fat cell size and insulin sensitivity assessed as M-value during clamp and as insulin action on glucose uptake in fat cells in vitro. This was seen in non-diabetic subjects after including age, sex and BMI in the analyses. No such relationship was found in type 2 diabetic subjects. In both groups, subcutaneous fat cell size correlated positively and independently with plasma levels of leptin but not to any of the other assessed adipokines. In nondiabetic subjects, omental fat cell size was independently and negatively correlated with insulin action in subcutaneous, but not omental, fat cells in vitro.Conclusions/interpretation Fat cell enlargement is associated with insulin resistance in non-diabetic individuals independently of BMI. This was not seen in type 2 diabetic subjects, suggesting that after development of type 2 diabetes other factors, not related to fat cell size, become more important for the modulation of insulin resistance.

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Section: Discussionsupporting

confidence: 59%

Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’

et al. 2007

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“…In addition it has been reported that IR is associated with increased plasma leptin concentration independent of the body fat. 10 Consistent with this hypothesis, previous studies have reported that OSA is independently associated with neuroendocrine dysregulation; in fact OSA has been reported to be bRIEF SUMMARY Current knowledge/Study Rationale: Impaired glucose tolerance is a common and important co-morbidity of obstructive sleep apnea yet its pathogenesis, beyond the shared etiology of obesity is unknown. Here we tested the hypothesis that OSA might induce increases of appetite regulating hormones which might suggest a cause for IGT.…”

Section: S C I E N T I F I C I N V E S T I G a T I O N Smentioning

confidence: 77%

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Patterson¹,

Twigg²,

Vazir³

et al. 2011

Journal of Clinical Sleep Medicine

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Study Objectives: Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghrelin, neuropeptide Y [NPY] and peptide tyrosine-tyrosine [PYY]). Method: We studied 68 OSA patients (mean AHI 22 events/h) and 37 age and weight matched healthy controls recruited by advertisement. All participants received a standardized evening meal, attended polysomnography and an oral glucose tolerance test (OGTT) on waking. Hormones were measured in blood taken before sleep (22:30) and at the start of the OGTT. Results: Impaired glucose tolerance was present in 54% of patients and 32% of controls (p = 0.05). The only differences between groups was that leptin was signifi cantly higher at 22:30 in OSA patients compared to controls (9.6 ng/L vs 7.9 ng/L, p = 0.05). OSA patients had marginally elevated plasma NPY levels at 22:30 (56.6 [52, 67] S C I E N T I F I C I N v E S T I G A T I O N SU ntreated obstructive sleep apnea (OSA) is associated with insulin resistance, 1,2 and some studies suggest that treatment with CPAP improves glucose control, 3,4 although this was not found in a randomized controlled trial of diabetics with sleep apnea. 5 The observation that established type 2 diabetics cannot improve glucose control when their OSA is treated with CPAP, emphasizes the importance of understanding the pathophysiology of insulin resistance associated with OSA.One mechanism linking OSA with impaired glucose tolerance could be sympathetic nerve activity which is a recognized phenomenon in OSA 6 ; indeed it has previously been hypothesized that this process is responsible for the elevated leptin levels seen in newly diagnosed OSA patients. 7 Consistent with this sibutramine, a serotonin and noradrenaline reuptake inhibitor, was able to improve insulin resistance in OSA independent of visceral fat. 8 Moreover two studies raise the hypothesis that hormones involved in appetite regulation could contribute to impaired glucose tolerance. Broglio et al. 9 demonstrated that ghrelin administered to healthy subjects simultaneously with glucose, resulted in a transient decrease of insulin concentration that was coupled with signifi cant increase in glucose levels. In addition it has been reported that IR is associated with increased plasma leptin concentration independent of the body fat. 10 Consistent with this hypothesis, previous studies have reported that OSA is independently associated with neuroendocrine dysregulation; in fact OSA has been reported to be bRIEF SUMMARY Current knowledge/Study Rationale: Impaired glucose tolerance is a common and important co-morbidity of obstructive sleep apnea yet its pathogenesis, beyond the shared etiology of obesity is unknown. Here we tested the hypothesis that OSA might induce increases of appetite regulating h...

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“…Because adiponectin is also directly related to body composition (25)(26), and this did not change with HRT, we would expect no change in adiponectin with HRT. Our finding of no change in adiponectin levels with HRT is consistent with a 6-month trial (45) and with a cross-sectional study (46).…”

Section: Commentmentioning

confidence: 99%

“…Leptin and adiponectin are hormones produced by fat that have been associated with amount of fat, insulin resistance, and the development of diabetes (23)(24)(25)(26). The effect of HRT on leptin is unclear, with some studies showing increases with HRT (27)(28)(29) and others finding either no change (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) or even a decrease with HRT (41)(42)(43)(44).…”

Section: Introductionmentioning

confidence: 99%

Insulin resistance with hormone replacement therapy: associations with markers of inflammation and adiposity

Cooper

Burger

Toth

et al. 2007

American Journal of Obstetrics and Gynecology

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Objective-To determine if insulin resistance associated with combination hormone replacement therapy (HRT) is mediated by changes in serum markers of inflammation or in serum adipocyte hormones.Study design-Forty-five postmenopausal women, aged 55 ± 7 years, were examined from a randomized, double-blind placebo-controlled trial evaluating the effect of HRT on insulin-stimulated glucose disposal and body composition. Volunteers were randomized to conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg vs. placebo for 1 year. At baseline and at 1 year, body composition was assessed by dual photon x-ray absorptiometry scans (DEXA); body fat distribution was measured by CT scans at the L4/L5 vertebral disc space; insulin sensitivity was measured by euglycemic hyperinsulinemic clamp; interleukin-6 (IL-6), leptin and adiponectin were measured by ELISA; and c-reactive protein (CRP) was measured by RIA.Results-HRT increased CRP by 121% compared to a 32% increase with placebo (p=0.03); HRT decreased glucose disposal by 17% compared to no change with placebo (p=0.04) as reported previously. HRT did not affect body composition, body fat distribution, IL-6, leptin, or adiponectin. The increase in CRP did not correlate with the decrease in glucose disposal in the HRT group (R=0.11, p=0.65).Conclusion-Treatment with HRT for one year increases CRP, but does not alter IL-6, adiponectin, or leptin. The change in CRP was not, however, related to the decrease in glucose disposal with HRT treatment.

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Relationship Between Insulin Sensitivity and Plasma Leptin Concentration in Lean and Obese Men

Cited by 388 publications

References 15 publications

Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’

Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Insulin resistance with hormone replacement therapy: associations with markers of inflammation and adiposity

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