scholarly journals Sitagliptin decreases visceral fat and blood glucoses in women with polycystic ovarian syndrome

2019 ◽  
Author(s):  
Jessica K. Devin ◽  
Hui Nian ◽  
Jorge E. Celedonio ◽  
Patricia Wright ◽  
Nancy J. Brown
Keyword(s):  
Body Composition ◽  
Half Life ◽  
Vascular Function ◽  
Polycystic Ovarian Syndrome ◽  
Interpulse Interval ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Glucose Response ◽  
Gh Secretion ◽  
Ovarian Syndrome

ContextWomen with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can increase visceral adiposity (VAT) and impair vascular function. GH releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion.ObjectiveWe tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS.MethodsEighteen women with PCOS participated in a double-blinded, cross-over study. They received sitagliptin 100 mg vs. placebo daily for one month separated by an eight-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT), assessment of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm.ResultsDuring OGTT, sitagliptin increased GLP-1 (p<0.001), early insulin secretion (from mean insulinogenic index 1.9±1.2 (SD) to 3.2±3.1; p=0.02) and decreased peak glucose (mean −17.2 mg/dL [95% CI −27.7, −6.6]; p<0.01). At one month, sitagliptin decreased VAT (from 1141.9±700.7 to 1055.1±710.1 g; p=0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9±3.6 to 17.0±6.8 min, N=16; p=0.04) and interpulse interval (from 53.2±20.0 to 77.3±38.2 min, N=16; p<0.05) but did not increase mean overnight GH (p=0.92 vs. placebo).ConclusionsSitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval.PrecisSitagliptin improved body composition and blood glucoses following oral glucose load in women with PCOS. Sitagliptin potentiated GH half-life but did not increase overnight GH levels.

scholarly journals Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome

2019 ◽  
Vol 105 (1) ◽  
pp. 136-151 ◽  
Author(s):  
Jessica K Devin ◽  
Hui Nian ◽  
Jorge E Celedonio ◽  
Patricia Wright ◽  
Nancy J Brown
Keyword(s):  
Half Life ◽  
Vascular Function ◽  
Polycystic Ovarian Syndrome ◽  
Interpulse Interval ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Gh Secretion ◽  
Ovarian Syndrome

Abstract Context Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired vascular function. GH-releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion. Objective We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS. Methods Eighteen women with PCOS participated in a double-blind, crossover study. They received sitagliptin either 100 mg or placebo daily for 1 month, with crossover treatments separated by an 8-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT) and assessments of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm. Results During OGTT, sitagliptin increased glucagon-like peptide-1 (P &lt; 0.001), early insulin secretion (from mean [± SD] insulinogenic index 1.9 ± 1.2 to 3.2 ± 3.1; P = 0.02), and decreased peak glucose (mean −17.2 mg/dL [95% CI, −27.7 to −6.6]; P &lt; 0.01). At 1 month, sitagliptin decreased VAT (from 1141.9 ± 700.7 to 1055.1 ± 710.1 g; P = 0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9 ± 3.6 to 17.0 ± 6.8 min, N = 16; P = 0.04) and interpulse interval (from 53.2 ± 20.0 to 77.3 ± 38.2 min, N = 16; P &lt; 0.05) but did not increase mean overnight GH (P = 0.92 vs placebo). Conclusions Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval. Clinical Trial Registration This study was registered at www.clinicaltrials.gov as NCT02122380 prior to enrollment of the first participant.

The Entero-Insular Axis in Polycystic Ovarian Syndrome

1996 ◽  
Vol 33 (3) ◽  
pp. 190-195 ◽  
Author(s):  
R Garaa ◽  
F Norris ◽  
J Wright ◽  
L Morgan ◽  
S Hampton ◽  
...  
Keyword(s):  
Polycystic Ovarian Syndrome ◽  
Gastric Inhibitory Polypeptide ◽  
Tolerance Test ◽  
Normal Weight ◽  
Immunoreactive Insulin ◽  
Oral Glucose ◽  
Hepatic Extraction ◽  
C Peptide ◽  
Molar Ratios ◽  
Ovarian Syndrome

We investigated the contributions made by the entero-insular axis, proinsulin and the fractional hepatic extraction of insulin to the hyperinsulinaemia characteristic of polycystic ovarian syndrome (PCOS). We measured plasma glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (7–36 amide) (GLP-17–36 amide), immunoreactive insulin (IRI), intact proinsulin (IPI), and C-peptide concentrations during a 75 g oral glucose tolerance test in seven normal weight women with PCOS and eight healthy women. Women with PCOS had higher fasting ( P = 0·05) and integrated ( P < 0·01) IRI concentrations than controls. Fasting C-peptide levels were similar in both groups but integrated C-peptide ( P < 0·05) concentrations were greater in PCOS subjects than controls. Fasting and integrated concentrations of glucose, GIP and GLP-17–36 amide were similar in subjects with PCOS and controls. Although fasting IPI concentrations were similar in both groups, integrated IPI concentrations were higher ( P = 0·05) in patients with PCOS. Women with PCOS had similar fasting but higher ( P <0·05) integrated IRI: C-peptide molar ratios than controls. Fasting and integrated IPI: IRI molar ratios were similar in both groups. These results confirm that lean women with PCOS have peripheral hyperinsulinaemia. The mild fasting hyperinsulinaemia is due to increased pancreatic secretion, whereas the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and reduced fractional hepatic extraction of insulin. Hyperproinsulinaemia is modest and appropriate in PCOS. GIP and GLP-17–36 amide do not contribute to the stimulated hyperinsulinaemia in PCOS.

scholarly journals A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Elena Passeri ◽  
Stefano Benedini ◽  
Elena Costa ◽  
Sabrina Corbetta
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Serum Alkaline Phosphatase ◽  
Resistance Index ◽  
Tolerance Test ◽  
Hepatic Insulin Resistance ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Glucose Response ◽  
Hepatic Insulin Sensitivity

Background. The RANKL/RANK/OPG signaling pathway is crucial for the regulation of osteoclast activity and bone resorption being activated in osteoporosis. The pathway has been also suggested to influence glucose metabolism as observed in chronic low inflammation.Aim. To test whether systemic blockage of RANKL by the monoclonal antibody denosumab influences glucose metabolism in osteoporotic women.Study Design. This is a prospective study on the effect of a subcutaneously injected single 60 mg dose of denosumab in 14 postmenopausal severe osteoporotic nondiabetic women evaluated at baseline and 4 and 12 weeks after their first injection by an oral glucose tolerance test.Results. A single 60 mg dose of denosumab efficiently inhibited serum alkaline phosphatase while it did not exert any significant variation in fasting glucose, insulin, or HOMA-IR at both 4 and 12 weeks. No changes could be detected in glucose response to the glucose load, Matsuda Index, or insulinogenic index. Nonetheless, 60 mg denosumab induced a significant reduction in the hepatic insulin resistance index at 4 weeks and in HbA1c levels at 12 weeks.Conclusions. A single 60 mg dose of denosumab might positively affect hepatic insulin sensitivity though it does not induce clinical evident glucose metabolic disruption in nondiabetic patients.

scholarly journals The shape of the glucose response curve during an OGTT heralds β−cell function in a large Chinese population

2019 ◽  
Author(s):  
Xinqi Cheng ◽  
Na Yang ◽  
Yuxiu Li ◽  
Qi Sun ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Population ◽  
Response Curve ◽  
Cell Function ◽  
Serum Insulin ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Glucose Response ◽  
Β Cell Function

Abstract Background The shape of the glucose response during an oral glucose tolerance test can detect β-cell function and insulin resistance. But there were few studies in Chinese, so we aimed to verify the utility of these connections in a large Chinese population. Methods A total of 11,866 times of 3-h OGTT were categorized to either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, Matsuda index, insulinogenic index and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results Individuals with a monophasic shape had significantly higher glucose, insulin, and had significantly lower insulin sensitivity and impaired β-cell function than multiphasic group. In addition, Individuals were younger with a multiphasic shape compared to those with a monophasic shape. Conclusion The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

The Effect of Lifestyle Intervention on Body Composition, Glycemic Control, and Cardiorespiratory Fitness in Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

2015 ◽  
Vol 25 (6) ◽  
pp. 533-540 ◽  
Author(s):  
Liza Haqq ◽  
James McFarlane ◽  
Gudrun Dieberg ◽  
Neil Smart
Keyword(s):  
Systematic Review ◽  
Body Composition ◽  
Lifestyle Intervention ◽  
Body Mass ◽  
Cardiorespiratory Fitness ◽  
Polycystic Ovarian Syndrome ◽  
Meta Analysis ◽  
Reproductive Age ◽  
Dietary Interventions ◽  
Ovarian Syndrome

Introduction:Polycystic ovarian syndrome (PCOS) affects 18–22% women of reproductive age. We conducted a systematic review and meta-analysis to quantify expected benefits of lifestyle (exercise and dietary) interventions on various clinical outcomes in PCOS.Methods:Potential studies were identified by conducting systematic search of PubMed, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane controlled trials registry (1966 to April 2013) using key concepts of PCOS, exercise, dietary and lifestyle interventions.Results:Significant improvements were seen in women who received lifestyle intervention vs. usual care, in body composition parameters of body mass index, mean difference (MD) = −0.12 kg.m−2 (95% CI [−0.22, −0.03], p = .009), body mass MD = −3.42 kg (95% CI [−4.86, −1.99], p < .00001), waist circumference MD = −1.64 cm (95% CI [−2.09, −1.19], p < .00001), waist−hip ratio MD = −0.03 (95% CI [−0.05, −0.01], p = .0002), and body fat % MD = −1.71% (95% CI [−3.10, −0.32], p = .02). Insulin did not improve, MD = −1.21 pmol/L (95% CI [−3.06, −0.63], p = .20). Lipid profile did not improve, total cholesterol MD = −0.02 mmol/L (95% CI [−0.25, 0.21], p = .89). C-reactive protein was significantly lower, MD = −0.47 mmol/L (95% CI [−0.80, −0.15], p = .004). Significant improvements were also observed in cardiorespiratory fitness with exercise alone reducing resting heart rate, MD = −1.89 beats.min−1 (95% CI [−2.90, −0.88], p = .0002), and peak VO2, MD = 4.86 ml.kg−1.min−1 (95% CI [2.83, 6.88], p < .00001). Lifestyle therapy also improved, peak VO2 MD = 5.09 ml.kg−1.min−1 (95% CI [3.13, 7.05], p < .00001).Conclusions:Our analyses suggest lifestyle intervention is optimal for improving body composition and cardiorespiratory fitness in women with PCOS.

scholarly journals The shape of the glucose response curve during an OGTT heralds β−cell function in a large Chinese population

2019 ◽  
Author(s):  
Xinqi Cheng ◽  
Na Yang ◽  
Yuxiu Li ◽  
Qi Sun ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Population ◽  
Response Curve ◽  
Cell Function ◽  
Serum Insulin ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Glucose Response ◽  
Β Cell Function

Abstract Background The shape of the glucose response during an oral glucose tolerance test can detect β-cell function and insulin resistance. But there were few studies in Chinese, so we aimed to verify the utility of these connections in a large Chinese population. Methods A total of 11,866 times of 3-h OGTT were categorized to either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, Matsuda index, insulinogenic index and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results Individuals with a monophasic shape had significantly higher glucose, insulin, and had significantly lower insulin sensitivity and impaired β-cell function than multiphasic group. In addition, Individuals were younger with a multiphasic shape compared to those with a monophasic shape. Conclusion The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

scholarly journals The shape of the glucose response curve during an OGTT heralds β−cell function in a large Chinese population

2019 ◽  
Author(s):  
Xinqi Cheng ◽  
Na Yang ◽  
Yuxiu Li ◽  
Qi Sun ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Population ◽  
Response Curve ◽  
Cell Function ◽  
Serum Insulin ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Glucose Response ◽  
Β Cell Function

Abstract Background The shape of the glucose response during an oral glucose tolerance test can detect β-cell function and insulin resistance. But there were few studies in Chinese, so we aimed to verify the utility of these connections in a large Chinese population. Methods A total of 11,866 times of 3-h OGTT were categorized to either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, Matsuda index, insulinogenic index and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results Individuals with a monophasic shape had significantly higher glucose, insulin, and had significantly lower insulin sensitivity and impaired β-cell function than multiphasic group. In addition, Individuals were younger with a multiphasic shape compared to those with a monophasic shape. Conclusion The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

Sign in / Sign up

Export Citation Format

Share Document