Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin resistance (IR) is ...connected with disturbances in switching between lipid and carbohydrate oxidation in response to insulin, called “metabolic inflexibility”. The aim of the present study was to estimate the whole-body insulin sensitivity, lipid and carbohydrate oxidation, metabolic flexibility in lean and obese PCOS women. The study group consisted of 92 women with PCOS, 40 lean (BMI<25 kg/m2) and 52 overweight or obesity (BMI>25 kg/m2), and 30 healthy normally menstruating women (14 lean and 16 overweight/obese) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Both the presence of PCOS (P<0.001) and obesity (P=0.005) were independently characterized by lower insulin sensitivity. PCOS (P=0.002) and obesity (P=0.001) independently predisposed to the lower non-oxidative glucose metabolism. Obese women had lower glucose oxidation (P=0.005) and higher lipid oxidation (P<0.001) in insulin-stimulated conditions in comparison to lean subject whereas PCOS had no effect on these parameters (P=0.29 and P=0.43; respectively). Metabolic flexibility was impaired in the obese (P=0.001) but it was not influenced by the presence of PCOS (P=0.78). Our data indicate that PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group.
Abstract. Irisin is an adipokine/myokine which could be connected with insulin sensitivity. Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, ...hyperandrogenism and insulin resistance. The aim of the present study was to determine the relationship between serum irisin concentration and insulin sensitivity (Mffm) as well as the effect of insulin infusion on circulating irisin levels in PCOS women as compared with healthy controls. Seventy seven women were enrolled in the study - 57 with PCOS and 20 healthy controls matched for BMI and age. Hyperinsulinemic euglycemic clamps were performed in all of the study participants. The serum concentrations of irisin at baseline and after the clamp, as well as changes of serum irisin concentration in response to insulin supplied during the clamp (Δirisin), were estimated. The mean serum concentrations of irisin at baseline and after hyperinsulinemia were higher in PCOS women in comparison to the control group (p=0.01 ; p=0.006, respectively). Insulin infusion resulted in a decrease of serum irisin concentration only in the PCOS group (p=0.007). In the control group, Δirisin positively correlated with Mffm (r=0.56, p=0.009). In the entire group, multiple regression analysis showed that Δirisin (β=0.70, p=0.0002), FFAs 60' during the clamp study (β=-0.22, p=0.01), SHBG (β=0.54, p<0.0001) and the interaction between Δirisin and PCOS (β=-0.67, p=0.0004) were significantly associated with Mffm. The higher serum irisin concentrations at baseline and in response to insulin infusion might be secondary to insulin resistant conditions in PCOS women.
ContextGhrelin is a peptide secreted mainly by the stomach, which has the ability to stimulate appetite and food intake. Serum ghrelin concentration decreases rapidly after a meal, probably because ...of the concurrent increase in serum insulin. Anorexia nervosa (AN) is an eating disorder, which is characterized by high serum ghrelin concentration; however, the regulation of circulating ghrelin by insulin in this disorder remains unclear.ObjectiveTo estimate serum ghrelin concentration in the fasting state and after hyperinsulinemia in women with AN.Design and participantsWe examined 19 women with AN, 26 lean healthy women, and 25 women who were overweight or obese. Serum ghrelin concentration was measured in the fasting state and after euglycemic hyperinsulinemic clamp.ResultsInsulin sensitivity was similar in AN and normal-weight women, and was markedly decreased in the obese subjects. In the fasting state, serum ghrelin was higher in AN group than in other groups (normal-weight, P=0.017; obese, P=0.0001) and in normal-weight women than in obese women (P=0.044). Hyperinsulinemia resulted in a marked decrease in serum ghrelin in AN (P<0.0001) and normal-weight women (P=0.002). The fall in serum ghrelin was higher in AN group than in other groups (normal-weight, P=0.0008; obese, P=0.0001), and was related to insulin sensitivity (r=0.24, P<0.05). In multiple regression analysis, only fasting serum ghrelin and the presence of AN were independent predictors of this fall.ConclusionsWomen with AN have an increased suppression of serum ghrelin by hyperinsulinemia. This phenomenon might lead to an increased and more rapid feeling of satiety in AN.
Dysglycemia is a public health challenge for the coming decades, especially in patients with chronic coronary syndromes (CCS). We want to assess the prevalence of undiagnosed diabetes mellitus (DM) ...and prediabetes, as well as identify factors associated with the development of dysglycaemia in patients with CCS. In total, 1233 study participants (mean age 69 ± 9 years), who, between 6 and 18 months earlier were hospitalized for acute coronary syndrome or elective revascularization, were examined (71.4% men). The diagnosis of DM, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) have been made according to World Health Organization (WHO) criteria. Based on the oral glucose tolerance test (OGTT) results, DM has been newly diagnosed in 28 (5.1%, mean age 69.9 ± 8.4 years) patients, 75% were male (
= 21). Prediabetes has been observed in 395 (72.3%) cases. IFG was found in 234 (42.9%) subjects, 161 (29.5%) individuals had IGT. According to multinomial logistic regression, body mass index (BMI) and high-density lipoprotein cholesterol (HDL-C) should be considered when assessing risk of development of dysglycaemia after discharge from the hospital. Among people with previously diagnosed DM, a significantly higher percentage were willing to change their lifestyles after the index event compared to other patients. Patients with chronic coronary syndromes suffer a very high frequency of dysglycaemia. Most patients with chronic coronary syndromes, especially those with high BMI or low HDL-C, should be considered for screening for dysglycemia using OGTT within the first year after hospitalization. A higher percentage of patients who were aware of their diabetic status changed their lifestyles, which added the benefit of timely diagnosis and treatment of diabetes.
Straczkowski et al examine the relationship between plasma IL-10 concentration and whole-body insulin sensitivity in apparently healthy humans. They demonstrate a significant positive association ...between circulating IL-10 levels and whole-body insulin sensitivity. IL-10 is also associated with other variables closely linked to insulin sensitivity, such as fasting and postload insulin concentrations, HDL cholesterol, and triglyceride levels.
Introduction. Data underline the role of betatrophin in glucose homeostasis. Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR). The aim of our study was to investigate the ...relationship of serum betatrophin concentrations with indirect indices of IR and insulin secretion in women with PCOS, compared to the control group. Methods. The study group comprised 43 women with PCOS and 16 controls. IR was assessed by HOMA-IR and Matsuda index. Insulin secretion was evaluated with HOMA-B. An oral glucose tolerance test (OGTT) with estimation of serum betatrophin concentrations was performed. Results. Glucose load resulted in an increase in serum betatrophin concentrations in the control group (p=0.02). Serum betatrophin concentrations at 120 min of OGTT were lower in women with PCOS than in the control group (p=0.02). We observed positive correlations between baseline serum betatrophin concentrations and HOMA-IR (r=0.39, p=0.008), negative correlations with Matsuda index (r=−0.31, p=0.004), and a positive relationship with HOMA-B (r=0.38, p=0.01) in women with PCOS. Multiple regression analysis revealed that HOMA-B (β=0.47, p=0.001) was an independent factor connected to serum betatrophin levels in PCOS. Conclusions. Serum concentrations of betatrophin are connected with insulin resistance and beta cell function and did not change after glucose load in women with PCOS.
Abstract Background Prandial premixed therapy 3 times daily has been proposed recently for type 2 diabetes mellitus (T2DM) patients who fail to achieve glycemic control with commonly used premixed ...insulin analogs, insulin lispro mix 75/25 (LM75/25) and biphasic insulin aspart 70/30 (BIAsp70/30) BID. Objective The aim of this work was to compare the efficacy and safety of 3-times daily insulin lispro mix 50/50 (TID group) with progressive titration of twice-daily LM75/25 or BIAsp70/30 (BID group) administered along with metformin in T2DM patients. Methods This was an open-label, 16-week, multicenter, randomized, parallel trial. End point glycosylated hemoglobin (HbA1c ) was the primary efficacy measure; HbA1c reduction from baseline to end point, percentage of patients reaching target HbA1c (<7.0% and ≤6.5%), postprandial blood glucose (BG), and BG excursions after lunch were secondary measures. Safety was evaluated by collecting adverse events. Results A total of 302 patients with mean (SD) age 57.7 (9.27) years, diabetes duration 11.2 (6.47) years, HbA1c 8.5% (1.23), fasting BG 184.0 (53.04) mg/dL, body weight 86.8 (14.79) kg, body mass index 31.7 (4.23) kg/m2 , and daily insulin dose ∼48 IU were randomized. No significant difference was observed in end point HbA1c between the 2 groups. Seven-point BG profiles showed lower fasting and postbreakfast BG in the BID group but lower postlunch BG in the TID group. Daily insulin dose change was similar in both groups, with more weight gain in the TID group ( P = 0.0009). Overall hypoglycemic rates were similar in both groups, but nocturnal hypoglycemia was more frequent in the BID group ( P = 0.0063). Conclusions In patients with T2DM who have not achieved adequate glycemic control with LM75/25 and BiAsp70/30 BID plus metformin and who are not candidates for basal bolus therapy, switching either to treatment with LM50/50 TID or to progressive titration of premix insulin analogs BID did not produce sufficient evidence of a difference of overall glycemic control between the 2 treatment groups. Short study duration and less intensive dose adjustments might have contributed to these results.
Soluble Tumor Necrosis Factor-α Receptors in Young Obese Subjects With Normal and Impaired Glucose Tolerance
Stella Dzienis-Straczkowska , MD ,
Marek Straczkowski , MD ,
Malgorzata Szelachowska , MD ...,
Agnieszka Stepien , PHD ,
Irina Kowalska , MD and
Ida Kinalska , MD
From the Department of Endocrinology, Diabetology and Internal Medicine, Medical Academy, Bialystok, Poland
Abstract
OBJECTIVE — Tumor necrosis factor-α (TNF-α) is a possible link between obesity and impaired glucose tolerance (IGT) and type 2 diabetes.
Data about TNF-α and soluble forms of its receptors (sTNFR1 and sTNFR2) in IGT are controversial. The aim of the present study
was to assess plasma TNF-α, sTNFR1, and sTNFR2 levels and to evaluate the relationships with insulin resistance in obese subjects
with IGT.
RESEARCH DESIGN AND METHODS — A total of 104 subjects participated in the present study: 30 obese subjects with IGT (obese-IGT), 32 obese subjects with
normal glucose tolerance (obese-NGT), and 42 lean healthy control subjects (control-NGT). Anthropometry and blood biochemical
parameters were measured and euglycemic-hyperinsulinemic clamp was performed.
RESULTS — Obese-IGT subjects were more insulin resistant in comparison with obese-NGT and control-NGT groups; obese-NGT subjects were
more insulin resistant than control-NGT. Plasma sTNFR1 and sTNFR2 were markedly higher in both groups of obese subjects in
comparison with control-NGT and in the obese-IGT versus obese-NGT group. Plasma sTNFR1 and sTNFR2 were inversely related to
insulin sensitivity. Both relationships remained significant after adjustment for age, BMI, waist girth, percent body fat,
plasma glucose, insulin, nonesterified fatty acids, cholesterol, and triglycerides. Correlation between sTNFR2 and insulin
sensitivity was also present in all the groups analyzed separately, but the correlation between sTNFR1 and insulin sensitivity
was present only in the obese-NGT group.
CONCLUSIONS — Our data suggest that TNF-α receptors are increased in obese-IGT subjects and are related to insulin resistance. These findings
indicate that the TNF-α system might contribute to the development of insulin resistance in glucose-intolerant subjects.
CRP, C-reactive protein
CV, coefficient of variation
ELISA, enzyme-linked immunosorbent assay
FM, fat mass
FFM, fat-free mass
HOMA-IR, homeostasis model assessment-insulin resistance
IGT, impaired glucose tolerance
NEFA, nonesterified fatty acid
obese-IGT, obese with IGT
obese-NGT, obese with normal glucose tolerance
TNF-α, tumor necrosis factor-α
WHR, waist-to-hip ratio
Footnotes
Address correspondence and reprint requests to Stella Dzienis-Straczkowska, MD, Department of Endocrinology, Diabetology and
Internal Medicine, Medical Academy, Bialystok, M.C. Sklodowskiej 24a, 15-276 Bialystok, Poland. E-mail: stellastraczkowska1{at}poczta.onet.pl .
Received for publication 28 July 2002 and accepted in revised form 11 December 2002.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
DIABETES CARE
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances ...including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract. Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin ...resistance (IR) is connected with disturbances in switching between lipid and carbohydrate oxidation in response to insulin, called "metabolic inflexibility". The aim of the present study was to estimate the whole-body insulin sensitivity, lipid and carbohydrate oxidation, metabolic flexibility in lean and obese PCOS women. The study group consisted of 92 women with PCOS, 40 lean (BMI<25 kg/m2) and 52 overweight or obesity (BMI>25 kg/m2), and 30 healthy normally menstruating women (14 lean and 16 overweight/obese) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Both the presence of PCOS (P<0.001) and obesity (P=0.005) were independently characterized by lower insulin sensitivity. PCOS (P=0.002) and obesity (P=0.001) independently predisposed to the lower non-oxidative glucose metabolism. Obese women had lower glucose oxidation (P=0.005) and higher lipid oxidation (P<0.001) in insulin-stimulated conditions in comparison to lean subject whereas PCOS had no effect on these parameters (P=0.29 and P=0.43; respectively). Metabolic flexibility was impaired in the obese (P=0.001) but it was not influenced by the presence of PCOS (P=0.78). Our data indicate that PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group.
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