Decreased Insulin Removal Contributes to Hyperinsulinemia in Obesity

Faber, O. K.; Christensen, K. C.; Kehlet, Henrik; Madsbad, Sten; Binder, Christian

doi:10.1210/jcem-53-3-618

Cited by 157 publications

(70 citation statements)

References 18 publications

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“…Fractional hepatic insulin exctraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide (14).…”

Section: Introductionmentioning

confidence: 99%

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion

Cucinelli¹,

Paparella²,

Soranna³

et al. 1999

European Journal of Endocrinology

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Objective: To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. Design: We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 mg/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added. Methods: During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment. Results: Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients. Conclusions: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.

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Section: Introductionmentioning

confidence: 99%

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion

Cucinelli¹,

Paparella²,

Soranna³

et al. 1999

European Journal of Endocrinology

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“…H yperinsulinemia is a characteristic feature of obesity (1,2). Several studies have shown that insulin hypersecretion (2,3) and impaired insulin clearance are main mechanisms for the increased plasma insulin levels found in obese patients (4). In a study of 14 lean subjects and 15 moderately obese patients, Polonsky et al (3) used the C-peptide deconvolution method (5) and intravenous glucose infusions to quantitate the contribution of insulin secretion and insulin clearance to plasma insulin levels.…”

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confidence: 99%

β-Cell Function in Morbidly Obese Subjects During Free Living

et al. 2005

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Insulin hypersecretion and insulin resistance are physiologically linked features of obesity. We tested whether extreme hypersecretion impairs ␤-cell function under free-living conditions and whether major weight loss modifies insulin hypersecretion, insulin sensitivity, and ␤-cell function. Plasma glucose, C-peptide, and free fatty acid concentrations were measured at hourly intervals during 24 h of normal life (including caloriestandardized meals) in 20 morbidly obese nondiabetic patients (BMI 48.4 ؎ 1.7 kg/m 2 ) and 7 nonobese ageand sex-matched control subjects; 8 of the obese patients were restudied 6 months and 2 years following biliopancreatic diversion. Insulin secretion was reconstructed from C-peptide levels by deconvolution and related to concurrent glucose levels through a mathematical model incorporating key features of ␤-cell function: rate sensitivity, ␤-cell glucose sensitivity, and potentiation. Insulin sensitivity (by the euglycemic insulin clamp technique) was reduced by 50% in obese subjects (23.1 ؎ 2.5 of obese subjects vs. 52.9 ؎ 4.9 mol ⅐ min ؊1 ⅐ kg FFM ؊1 of control subjects, means ؎ SE, P ‫؍‬ 0.0004) as was mean 24-h insulin clearance (median 809 [interquartile range 451] vs. 1,553 [520] ml ⅐ min ؊1 ⅐ m ؊2 , P < 0.001) due to a 50% reduction in hepatic insulin extraction (P < 0.01). Over 24 h, insulin secretion was doubled in obese subjects (468 nmol [202] H yperinsulinemia is a characteristic feature of obesity (1,2). Several studies have shown that insulin hypersecretion (2,3) and impaired insulin clearance are main mechanisms for the increased plasma insulin levels found in obese patients (4). In a study of 14 lean subjects and 15 moderately obese patients, Polonsky et al. (3) used the C-peptide deconvolution method (5) and intravenous glucose infusions to quantitate the contribution of insulin secretion and insulin clearance to plasma insulin levels. They found that under basal fasting conditions, hypersecretion contributes more than reduced insulin clearance to the genesis of hyperinsulinemia. In the same group of subjects, these authors also evaluated the 24-h profile of insulin secretion (6). They found that whereas insulin secretion was higher than in lean subjects throughout 24 h, the temporal pattern of secretion was unaltered in obese subjects, suggesting that the functional ␤-cell mass was expanded but regulatory mechanisms were still operative. Detailed analyses of the relationship between insulin hypersecretion and the concomitant plasma glucose concentrations under free-living conditions and between insulin hypersecretion and insulin resistance, however, have not been carried out.Morbid obesity, such as is seen in relatively young subjects, may be a partially different condition from the overweight and moderate obesity more often developing after the 4th decade of life (7). For example, in morbidly obese subjects, the cardiovascular risk factor profile is frequently quite favorable despite the accumulation of Ͼ40 kg of excess fat (8). Although it can be presumed that se...

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“…Several studies reported that insulin resistance explains the strong association between obesity and hypertension (17, 1 8). Hyperinsulinemia, which may be due to insulin resistance and reduced insulin clearance, was also found in obesity and hypertension (5)(6)(7)(8). Therefore, insulin is considered to cause BPelevation by stimulating sodium reabsorption (19) and activation of the sympathetic nervous system in obesity (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Euglycemic insulin clamp procedure Since this method has been previously described in detail (1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14], only the general procedure will be outlined here.…”

Section: Blood Pressurementioning

confidence: 99%

“…The prevalence of obesity is, similarly, much greater among hypertensives than among normotensives. It is well knownin Western societies that insulin resistance and impaired insulin clearance are commonpathophysiological features in both obesity and hypertension (5)(6)(7)(8). However, no correlation between high blood pressure (BP) and hyperinsulinemia was found in obese subjects by Grugni et al (9).…”

Section: Introductionmentioning

confidence: 99%

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Relationship between Insulin and Blood Pressure in Japanese Obese Subjects.

et al. 1999

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Object: The association of obesity and hypertension is well recognized. However, the nature of the relationship between increased body weight and blood pressure (BP) elevation has remained obscure. Patients and Methods: Weevaluated BP, insulin sensitivity, insulin clearance and fasting plasma insulin concentration in 19 younger (over 40 years) and in 15 older (more than 40 years) obese subjects to determine the relationships between BP and other factors. Insulin sensitivity and clearance were determined with the euglycemic clamp technique. Results: BP was not associated with insulin sensitivity although most of the subjects showed insulin resistance. In the younger obese group, a positive correlation between diastolic BPand body mass index (kg/m2) was found (r=0.740; p=0.043). In the older obese group, systolic and diastolic BPwere correlated with fasting plasma insulin levels (r=0.705; p=0.003; r=0.574; p=0.025, respectively), and systolic BP was inversely correlated with insulin clearance (r=-0.715, p=0.003). Conclusion: These results suggest that insulin is an important factor in BP elevation in older obese subjects, but not in younger obese subjects. (Internal Medicine 38: 467-471, 1999)

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Decreased Insulin Removal Contributes to Hyperinsulinemia in Obesity

Cited by 157 publications

References 18 publications

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion

β-Cell Function in Morbidly Obese Subjects During Free Living

Relationship between Insulin and Blood Pressure in Japanese Obese Subjects.

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