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

1999 ◽  
pp. 215-223 ◽  
Author(s):  
F Cucinelli ◽  
P Paparella ◽  
L Soranna ◽  
A Barini ◽  
B Cinque ◽  
...  

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 micrograms/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.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Karla A Temple ◽  
Babak Mokhlesi ◽  
Jason R Carter ◽  
Harry Whitmore ◽  
Eve Van Cauter ◽  
...  

Abstract The prevalence of prediabetes and diabetes is substantially higher in PCOS women with obstructive sleep apnea (OSA) compared to PCOS women without OSA1,2,3. Prior studies, however, did not examine the complex interaction between race and OSA on metabolic function in PCOS. We sought to determine if the impact of OSA on glucose and insulin metabolism is affected by race. We studied non-Hispanic white (NHW) (n=53) and African-American (AA) (n=48) women with PCOS. Following an overnight polysomnogram (PSG), PCOS women (NHW without OSA n=40; NHW with OSA n=13; AA without OSA n=36; AA with OSA n=12) had a 2-h 75-g oral glucose tolerance test (OGTT) with blood sampling every 30 minutes for measurement of glucose, insulin, and C-peptide concentrations. OSA severity was measured by the Apnea-Hypopnea Index (AHI). Only women without OSA (AHI &lt; 5) or with moderate-to-severe OSA (AHI &gt; 15) were included in these analyses; women with mild OSA were excluded. Insulin secretion rates (ISR) during the OGTT were derived by deconvolution of C-peptide levels 4. Area under the curve (AUC) response to the glucose challenge was calculated using the trapezoidal method. BMI and age did not differ between races in PCOS women without OSA (BMI [kg/m2]: 36.3±1.2 vs. 37.2±1.1, p=0.58; Age [yr]: 27.7±0.8 vs. 27.2±0.8, p=0.65; for NHW and AA respectively), or in PCOS women with OSA (BMI [kg/m2]: 42.8±1.7 vs. 44.7±2.0, p=0.50; Age [yr]: 31.4±1.6 vs. 28.6±1.6, p=0.18; for NHW and AA respectively). OSA severity was similar in NHW and AA PCOS women without OSA (AHI: 1.5±0.2 vs 2.1±0.2, p=0.076), and PCOS women with OSA (AHI: 32.0±4.9 vs. 28.3±4.4, p=0.26). Higher glucose responses during the OGTT were observed in NHW PCOS women with OSA compared to both NHW (AUC: 18,965±648 vs. 15,797±371, p=0.0004) and AA (AUC: 18,965±648 vs. 15,801±497, p=0.0005) PCOS women without OSA. Glucose responses did not differ significantly between AA PCOS women with OSA and AA PCOS women without OSA (AUC: 17,104±965 vs. 15,801±497, p=0.15). Similarly, ISR was higher in NHW PCOS women with OSA compared to both NHW (AUC: 5,648±488 vs. 3,907±231, p=0.0006) and AA (AUC: 5,648±488 vs. 3,981±235, p=0.0011) PCOS women without OSA. ISR did not differ significantly between AA PCOS women with OSA and AA PCOS women without OSA (AUC: 4,827±461 vs. 3,981±235, p=0.09). CONCLUSIONS: OSA has a greater impact on glucose and ISR during an oral glucose challenge in NHW compared to AA women with PCOS. Future studies would benefit from including race when evaluating metabolic outcomes in women with PCOS. References: 1Fogel et al., J Clin Endocrinol Metab. 2001: 86:1175–1180. 2Kapsimalis et al., Sleep. 2002; 25:499–506. 3Kapsimalis et al., Sleep. 2002; 25:412–419. 4Polonsky et al., J Clin Invest. 1986 Jan; 77(1):98–105.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1275-1275
Author(s):  
Magdalena Sevilla ◽  
Donaji Gomez-Velasco ◽  
Ivette Cruz-Bautista ◽  
Laura Lazaro-Carrera ◽  
Paloma Almeda-Valdes ◽  
...  

Abstract Objectives A haplotype in SLC16A11 is associated with decreased insulin action, and risk for type 2 diabetes (T2D) in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D. Methods We recruited subjects with at least one prediabetes criteria according to the American Diabetes Association, and body mass index 25–45 kg/m2. Subjects were randomized in two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids and 15% protein sources + physical activity (&gt;150 min medium intensity per week), or LSI + metformin (750 mg prolonged release twice a day). Interventions were prescribed by standardized dietitians. The goal was to achieve &gt;3% weight loss. We evaluated the early treatment response in a follow-up period of 12 weeks with intermediate visits each 3 weeks to reinforce knowledge and treatment goals. Evaluations (baseline and post-treatment) included an oral glucose tolerance test (OGTT), and dual-energy X-ray absorptiometry. Adherence to treatment was measured trough electronic recordings. Participants were genotyped for the risk allele rs13342232. Researchers remained blinded to the genotype results. The effects of the risk haplotype were evaluated with linear and logistic regressions adjusted by age, sex, and baseline body fat %. Results We evaluated 61 subjects, 30 carriers, and 31 non-carriers. Most of participants (57%) achieved ≥3% weight loss. The LSI + metformin treatment increased in carriers, 2 times OR 3 IC95% (1.07 – 8.6) (P = 0.04) the probability to reach the ≥3% weight loss goal compared with LSI and non-carriers. In the same treatment, carriers had a greater decrease in the total and incremental area under the curve of insulin in the OGTT IC95% (−1.75 −0.11) (P = 0.02) compared with non-carriers and LSI. Carriers also had higher decrease in postprandial glucose compared with non-carriers regardless of treatment −12.63 + 30.38 vs 0.71 30.24 (P = 0.02). Conclusions After 12 weeks of treatment, carriers with prediabetes showed a higher probability achieve weight loss and to improve insulin secretion with metformin. Regardless of the treatment, carriers were prone to improve postprandial glucose. Funding Sources Miguel Aleman Medical Research Award.


2008 ◽  
Vol 159 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Jana Vrbikova ◽  
Martin Hill ◽  
Bela Bendlova ◽  
Tereza Grimmichova ◽  
Katerina Dvorakova ◽  
...  

ObjectivePolycystic ovary syndrome (PCOS) has been linked to a high risk of type 2 diabetes mellitus. Disturbances in the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been observed in states with impaired glucose regulation. This paper considers the secretion of GIP and GLP-1 after oral glucose load in a group of lean, glucose-tolerant PCOS women in comparison with age- and body mass index (BMI)-matched healthy women.DesignCase control.MethodsPCOS (n=21, 25.8±4.1 years, BMI 21.6±1.7 kg/m2) and control healthy women (CT, n=13, 28.5±7.2 years, BMI 20.3±2.5 kg/m2) underwent oral glucose tolerance test (OGTT) with blood sampling for glucose, insulin, C-peptide, total GIP, and active GLP-1. Insulin sensitivity was determined both at fasting and during the test.StatisticsRepeated measures ANOVA.ResultsGlucose levels and insulin sensitivity did not differ between PCOS and CT. PCOS had significantly higher levels of C-peptide (P<0.05) and tended to have higher insulin levels. The levels of total GIP were significantly higher in PCOS than in CT (P<0.001). Active GLP-1 levels exhibited a significantly different time-dependent pattern in PCOS (P<0.002 for PCOS versus time interaction). GLP-1 concentrations were similar in PCOS and CT in the early phase of OGTT and then reached significantly lower levels in PCOS than in CT at 180 min (P<0.05).ConclusionsIncreased total GIP and lower late phase active GLP-1 concentrations during OGTT characterize PCOS women with higher C-peptide secretion in comparison with healthy controls, and may be the early markers of a pre-diabetic state.


2016 ◽  
Vol 5 (6) ◽  
pp. 44-52 ◽  
Author(s):  
L Bahler ◽  
H J Verberne ◽  
E Brakema ◽  
R Tepaske ◽  
J Booij ◽  
...  

Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening) results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC) 742 mmol/L * 120 min (695–818) vs 641 (504–750), P = 0.036, AUC for insulin did not change, P = 0.575). In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236–96,831) vs 36,448 (25,213–57,711), P = 0.012) and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614–988) vs 644 (568–829), P = 0.017) and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration.


2019 ◽  
Vol 8 (4) ◽  
pp. 479 ◽  
Author(s):  
Maitane Izaguirre ◽  
Javier Gómez-Ambrosi ◽  
Amaia Rodríguez ◽  
Beatriz Ramírez ◽  
Sara Becerril ◽  
...  

Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.


2013 ◽  
Vol 168 (4) ◽  
pp. 515-523 ◽  
Author(s):  
Sarah Chouinard-Castonguay ◽  
S John Weisnagel ◽  
André Tchernof ◽  
Julie Robitaille

BackgroundFew studies have investigated whether favorable effects of lactation persist after weaning and protect women with prior gestational diabetes mellitus (GDM) against later development of insulin resistance and insulin secretion defects.ObjectiveTo investigate the impact of lactation duration on insulin and glucose response among women with prior GDM.Design/methodsThe study group comprised 144 women with a history of GDM between 2003 and 2010. Plasma insulin and glucose concentrations were obtained from a 75 g oral glucose tolerance test (OGTT). Total lactation duration (exclusive breastfeeding and breast and bottle-feeding) for all infants was self-reported in months.ResultsMean age was 36.5±5.0 years. Time between delivery and metabolic testing was 4.0±1.9 years. Women breastfed for an average of 13.9±16.8 months. Most women (80.6%) reported a history of lactation. Women who lactated had higher homeostasis model assessment for insulin sensitivity (HOMA-IS) and Matsuda indices and lower fasting and 2-h post-OGTT insulin concentrations as well as area under the curve (AUC) for insulin (P≤0.01 for all). Compared with women who lactated for <10 months, women who lactated for ≥10 months had improved insulin sensitivity–secretion index, higher HOMA-IS and Matsuda indices, lower fasting and 2-h post-OGTT insulin concentrations as well as AUC for insulin, and lower incidence of impaired glucose intolerance (P≤0.05 for all). In multiple linear regression analyses, lactation duration emerged as an independent predictor of fasting insulin concentrations (β=−0.02) and insulin sensitivity indices (β=0.02) (P≤0.05 for all).ConclusionsThese results suggest that longer duration of lactation is associated with improved insulin and glucose response among women with prior GDM.


2016 ◽  
Vol 121 (3) ◽  
pp. 724-729 ◽  
Author(s):  
Lisa Chu ◽  
Katherine M. Morrison ◽  
Michael C. Riddell ◽  
Sandeep Raha ◽  
Brian W. Timmons

The capacity to match carbohydrate (CHO) utilization with availability is impaired in insulin-resistant, obese adults at rest. Understanding exogenous carbohydrate (CHOexo) oxidation during exercise and its association to insulin resistance (IR) is important, especially in children at risk for type 2 diabetes. Our objective was to examine the oxidative efficiency of CHOexo during exercise in obese children with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Children attended two visits and were identified as NGT ( n = 22) or IGT ( n = 12) based on 2-h oral glucose tolerance test (OGTT) glucose levels of <7.8 mmol/l or ≥7.8 mmol/l, respectively. Anthropometry, body composition, and aerobic fitness (V̇o2max) were assessed. Insulin and glucose at baseline, 30, 60, 90, and 120 min during the OGTT were used to calculate measures of insulin sensitivity. On a separate day, a 13C-enriched CHO drink was ingested before exercise (3 × 20 min bouts) at 45% V̇o2max. Breath measurements were collected to calculate CHOexo oxidative efficiency. CHOexo oxidative efficiency during exercise was similar in IGT (17.0 ± 3.6%) compared with NGT (17.1 ± 4.4%) ( P = 0.90) despite lower whole body insulin sensitivity in IGT at rest ( P = 0.02). Area under the curve for insulin (AUCins) measured at rest during the OGTT was greater in IGT compared with NGT ( P = 0.04). The ability of skeletal muscle to utilize CHOexo was not impaired during exercise in children with IGT.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2650 ◽  
Author(s):  
Daniel E. Newmire ◽  
Eric Rivas ◽  
Sarah E. Deemer ◽  
Darryn S. Willoughby ◽  
Victor Ben-Ezra

Background: The ingestion of whey protein and amino acids with carbohydrate (CHO) enhances the release of glucagon-like peptide-1 (GLP-1) and glucose-dependent-insulinotropic peptide (GIP) that promote insulin secretion. It is unknown if L-isoleucine (Ile) and L-leucine (Leu) have this same effect. The purpose of this study was to examine how Ile and Leu influence both GLP-1 and GIP, subsequent pancreatic hormones, and glycemia in healthy, inactive adults. Methods: Twelve adults (6F/6M; age 27.4 ± 2 years; BMI 26.3 ± 2 kg/m2; lean body mass 53.2 ± 5 kg; body fat 34.1 ± 3%) completed four conditions in a randomized, cross-over fashion. Treatments standardized (0.3 g/kg·LBM−1) (1) Leu, (2) Ile, (3) Equal (1:1 g) of Leu + Ile, and (4) placebo (Pla, 3.5 g inert stevia) ingested 30 min prior to an oral glucose tolerance test (OGTT). Samples of plasma glucose, insulin, glucagon, GIPTotal, and GLP-1Active were assessed. Results: A treatment (p = 0.01) effect comparing Ile vs. Leu (p = 0.02) in GIPTotal. Area under the curve showed an increase in GIPTotal from Ile compared to Leu and Pla (p = 0.03). No effect was found on GLP-1. The ingestion of Ile prior to CHO augmented GIP concentration greater than Leu or Pla. No correlation was found between GIP, insulin, and glucose between conditions. Conclusions: Ile impacts GIP concentration, which did not relate to either insulin or glucose concentrations. Neither Ile, nor Leu seem to have an effect on hyperglycemia ingested prior to a CHO drink.


2020 ◽  
Vol 30 (2) ◽  
pp. 139-144
Author(s):  
Emma L. Sweeney ◽  
Daniel J. Peart ◽  
Irene Kyza ◽  
Thomas Harkes ◽  
Jason G. Ellis ◽  
...  

Experimental sleep restriction (SR) has demonstrated reduced insulin sensitivity in healthy individuals. Exercise is well-known to be beneficial for metabolic health. A single bout of exercise has the capacity to increase insulin sensitivity for up to 2 days. Therefore, the current study aimed to determine if sprint interval exercise could attenuate the impairment in insulin sensitivity after one night of SR in healthy males. Nineteen males were recruited for this randomized crossover study which consisted of four conditions—control, SR, control plus exercise, and sleep restriction plus exercise. Time in bed was 8 hr (2300–0700) in the control conditions and 4 hr (0300–0700) in the SR conditions. Conditions were separated by a 1-week entraining period. Participants slept at home, and compliance was assessed using wrist actigraphy. Following the night of experimental sleep, participants either conducted sprint interval exercise or rested for the equivalent duration. An oral glucose tolerance test was then conducted. Blood samples were obtained at regular intervals for measurement of glucose and insulin. Insulin concentrations were higher in SR than control (p = .022). Late-phase insulin area under the curve was significantly lower in sleep restriction plus exercise than SR (862 ± 589 and 1,267 ± 558; p = .004). Glucose area under the curve was not different between conditions (p = .207). These findings suggest that exercise improves the late postprandial response following a single night of SR.


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