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Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.
Yang, H, Lin, J, Li, H, Liu, Z, Chen, X, Chen, Q
Frontiers in endocrinology. 2021;:571229
Abstract
BACKGROUND Our study aimed to investigate if serum prolactin (PRL) levels associated with insulin resistance and beta-cell dysfunction in infertile patients with polycystic ovary syndrome (PCOS). METHODS This was a retrospective cross-sectional study performed in the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University. From January 2007 to August 2018, a total of 792 PCOS and 700 non-PCOS infertile women were included. All patients' prolactin levels were in the normal range. PCOS was diagnosed according to the Rotterdam Criteria. Anthropometric parameters, blood pressure, serum prolactin levels, sex hormones, fasting lipids, fasting plasma glucose (FPG), fasting insulin (FINS) and hepatic biological parameters were measured in all subjects. RESULTS Serum prolactin levels in PCOS women were significantly decreased compared with levels in non-PCOS women after adjusting for age and BMI (P < 0.05). Moreover, we found that prolactin levels were positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with age, BMI, waist circumference (WC), hip circumference (HC), luteinizing hormone/follicle stimulating hormone (LH/FSH), estradiol (E2), FINS, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β (HOMA-β), triglyceride (TG) and alanine aminotransferase (ALT) (P < 0.05). After adjusting for age and BMI, multiple linear regression analysis revealed that LH, LH/FSH, E2, FINS, HOMA-IR, and HOMA-β were negatively associated with serum PRL (P < 0.05). CONCLUSIONS Low serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.
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Insulin Resistance is Associated with Central Pain in Patients with Fibromyalgia.
Pappolla, MA, Manchikanti, L, Candido, KD, Grieg, N, Seffinger, M, Ahmed, F, Fang, X, Andersen, C, Trescot, AM
Pain physician. 2021;(2):175-184
Abstract
BACKGROUND Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. IR has been associated with multiple conditions, including chronic pain. Fibromyalgia (FM) is one of the common generalized chronic painful conditions with an incidence rate affecting 3% to 6% of the population. Substantial interest and investigation into FM continue to generate many hypotheses.The relationship between IR and FM has not been explored. IR is known to cause abnormalities in the cerebral microvasculature, leading to focal hypoperfusion. IR also has been shown to cause cognitive impairment in FM patients, as in parkinsonism. As demonstrated by advanced imaging methods, similar brain perfusion abnormalities occur in the brain of patients with FM as with IR. OBJECTIVES To determine the potential association between FM and IR. SETTING Subspecialty pain medicine clinics. STUDY DESIGN Observational cross-sectional study. METHODS Laboratory data was extracted through a retrospective review of medical records from patients who had met the American College of Rheumatology (ACR) criteria for FM. The Hemoglobin A1c (HbA1c) values from 33 patients with FM were compared with the means of the glycated HbA1c levels of 2 control populations. In addition, established indices of IR [Quantitative Insulin Sensitivity Check Index (QUICKI) and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)] were calculated in a subgroup of patients in whom the analytes necessary for these calculations were available. To assess for confounding factors, the associations between HbA1c, QUICKI, HOMA-IR, fasting insulin levels, and glucose, after controlling for age, were explored by multiple analyses of variance with relation to gender and ethnicity. RESULTS We found an association between IR and FM that was independent of age, gender, and ethnicity. We found that patients with FM belong to a distinct population that can be segregated from the control groups by their HbA1c levels, a surrogate marker of IR. This was demonstrated by analyzing the data after introducing an age correction into a linear regression model. This strategy showed significant differences between patients with FM and control subjects (P < 0.0001 and P = 0.0002, for 2 separate control populations, respectively). A subgroup analysis using the QUICKI and HOMA-IR showed that all patients with FM in this subgroup (100%) exhibited laboratory abnormalities pointing to IR. LIMITATIONS Small observational cross-sectional study. There are also intrinsic limitations that are attributed to cross-sectional studies. CONCLUSION The association demonstrated in this study warrant further investigation, including the pursuit of randomized, double-blind clinical trials to determine the effect of improving insulin sensitivity in FM related pain scores. Such studies could unveil a potential pathogenetic relationship between FM, central pain, and IR. Based on these initial findings, we present the hypothesis that IR may underlie pathological mechanisms leading to central pain. If confirmed, this may lead to a paradigm shift in the management of central pain.
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Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men.
Kiya, M, Tamura, Y, Takeno, K, Someya, Y, Kakehi, S, Sato, M, Yamasaki, N, Kadowaki, S, Suzuki, R, Furukawa, Y, et al
The Journal of clinical endocrinology and metabolism. 2021;(5):e2228-e2238
Abstract
CONTEXT Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians. DESIGN AND SETTING To investigate the relationships between decreased AN level, impaired ATIS, and metabolic abnormalities, we studied 94 Japanese men whose body mass index was less than 25 kg/m2. We divided the subjects into 4 groups based on their median AN level and ATIS, the latter calculated as the degree of insulin-mediated suppression of free fatty acids during hyperinsulinemic euglycemic clamp, and compared the metabolic parameters in the 4 groups. RESULTS The High-ATIS/High-AN group (n = 29) showed similar anthropometric data to the High-ATIS/Low-AN group (n = 18). In contrast, both the Low-ATIS/High-AN (n = 18) and Low-ATIS/Low-AN (n = 29) groups showed significantly lower muscle insulin sensitivity than the High-ATIS groups. The intrahepatic lipid level in the Low-ATIS/Low-AN group was significantly higher than that in the High-ATIS groups. In addition, the Low-ATIS/Low-AN group had a significantly higher fasting serum triglyceride level and significantly lower high-density lipoprotein cholesterol level than the other 3 groups. CONCLUSIONS In nonobese Japanese men with high ATIS, the AN level was not associated with metabolic characteristics. On the other hand, subjects with low ATIS showed reduced muscle insulin sensitivity, and those with a decreased AN level demonstrated multiple metabolic abnormalities, represented by fatty liver and dyslipidemia.
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Insulin Resistance Adversely Affect IVF Outcomes in Lean Women Without PCOS.
Wang, H, Zhang, Y, Fang, X, Kwak-Kim, J, Wu, L
Frontiers in endocrinology. 2021;:734638
Abstract
OBJECTIVE To investigate the effects of insulin resistance (IR) on IVF outcomes and a potential underlying mechanism in lean women without PCOS. DESIGN A prospective cohort study at the University Clinic. SETTING IVF center at the University setting. PATIENTS A total of 155 lean women (body mass index <25) without PCOS undergoing IVF cycle. INTERVENTION Patients were allocated to IR and non-IR groups based on HOMA-M120. MAIN OUTCOME MEASURES IVF outcomes, including egg quality, the percentage of mature oocytes, fertilization rate, blastocyst formation rate, advanced embryo rate, and cumulative live birth rate were investigated. Auto-immune parameters, peripheral blood immunophenotypes, thyroid hormone, homocysteine, and 25-OH-vitamin D3 (25-OH-VD3) levels were analyzed. RESULTS The percentage of mature oocytes and blastocyst formation rate were significantly lower in the IR group as compared with those of the non-IR group (p<0.05, respectively). The proportion of peripheral blood CD19+ B cells was significantly higher in the IR group than those of the non-IR group (p<0.05). Homocysteine, 25-OH-VD3, and auto-immune parameters were the same between the two groups. CONCLUSION In lean infertile women without PCOS, IR is associated with the decreased percentage of mature eggs and poor embryo quality in which B cell immunity may play a role.
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Associations of Serum Fatty Acid Proportions with Obesity, Insulin Resistance, Blood Pressure, and Fatty Liver: The Cardiovascular Risk in Young Finns Study.
Kaikkonen, JE, Jula, A, Viikari, JSA, Juonala, M, Hutri-Kähönen, N, Kähönen, M, Lehtimäki, T, Raitakari, OT
The Journal of nutrition. 2021;(4):970-978
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BACKGROUND The links between fatty acids (FAs) and cardiometabolic outcomes are topics of debate. OBJECTIVE Our aim was to investigate the associations between serum standardized FA percentages and cardiometabolic outcomes. METHODS We used cross-sectional (n = 2187-2200 subjects, age 24-39 y, women 54%) and 10-year prospective data (n = 975-1414 subjects) from the Young Finns Study. Outcomes included prevalent and incident obesity, insulin resistance (HOMA-IR index in the upper quintile), elevated blood pressure (BP; taking medication, or diastolic or systolic BP in the upper quintile), and incident nonalcoholic fatty liver. Logistic regression models were used to calculate ORs per SD increase in fatty acids (FAs). The models were adjusted for age and sex, and additionally for other potential confounders. RESULTS Several cross-sectional findings were also statistically significant in prospective models (Bonferroni corrected P < 0.003). In fully-adjusted models for obesity, these consisted of SFAs (OR: 1.28) and MUFAs (OR: 1.38), including palmitoleic (OR: 1.39) and oleic acids (OR: 1.37). Furthermore, PUFAs (OR: 0.70), including linoleic (OR: 0.67) and docosahexaenoic acids (OR: 0.75), were inversely related with obesity, whereas γ-linolenic acid (OR: 1.32) was positively associated with obesity. In age- and sex-adjusted models for insulin resistance, MUFAs (OR: 1.26) and oleic acid (OR: 1.25) were positively, and PUFAs (OR: 0.81), particularly linoleic acid (OR: 0.78), were inversely associated with HOMA-IR. Similarly with elevated BP, palmitic acid (OR: 1.22), MUFAs (OR: 1.28), and oleic acid (OR: 1.28) were positively associated with elevated BP, whereas PUFAs (OR: 0.77), n-6 (omega-6) PUFAs (OR: 0.79), and linoleic acid (OR: 0.77) were inversely associated. In fully-adjusted models for incident fatty liver, the most consistent predictors were high palmitic (OR: 1.61) and low linoleic acid (OR: 0.63) percentages. The n-6/n-3 (omega-3) PUFA ratio was not linked with any adverse outcomes. CONCLUSIONS High serum percentages of total SFAs and MUFAs and low PUFAs, but also several specific FAs, predict future unfavorable cardiometabolic outcomes in Finnish adults.
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The ratio of estimated average glucose to fasting plasma glucose level as an indicator of insulin resistance in young adult diabetes: An observational study.
Guo, J, Lei, S, Zhou, Y, Pan, C
Medicine. 2020;(40):e22337
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At present, glycated hemoglobin (HbA1c) and glycated albumin (GA) are used to evaluate glycemic control in diabetic patients, but they cannot reflect insulin deficiency and/or insulin resistance.We investigated the feasibility of using estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to estimate insulin resistance in young adult diabetes. A total of 387 patients with type 2 diabetes were included and were stratified into 2 groups based on median values of the glycemic index ratio: the GA/A1c ratio <2.09 (n = 91) and ≥2.09 (n = 296); the eAG/fPG ratio <1.69 (n = 155) and ≥1.69 (n = 232). HbA1c, GA, fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c was calculated, and the homeostasis model assessment of β-cell function and insulin resistance were determined. The homeostasis model assessment of insulin resistance level was significantly associated with the eAG/fPG ratio, but not with the ratio of GA to HbA1c, GA, HbA1c, and fructosamine levels. The ratio of estimated average glucose to fasting plasma glucose level correlates with insulin resistance in young adult diabetes.
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The Macrophage Activation Marker Soluble CD163 is Longitudinally Associated With Insulin Sensitivity and β-cell Function.
Semnani-Azad, Z, Connelly, PW, Johnston, LW, Retnakaran, R, Harris, SB, Zinman, B, Hanley, AJ
The Journal of clinical endocrinology and metabolism. 2020;(3):e285-94
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CONTEXT Chronic inflammation arising from adipose tissue macrophage (ATM) activation may be central in type 2 diabetes etiology. Our objective was to assess the longitudinal associations of soluble CD163 (sCD163), a novel biomarker of ATM activation, with insulin sensitivity, β-cell function, and dysglycemia in high-risk subjects. METHODS Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 408). Levels of sCD163 were measured using fasting serum. Insulin sensitivity was assessed by HOMA2-%S and the Matsuda index (ISI). β-cell function was determined by insulinogenic index (IGI) over HOMA-IR and insulin secretion-sensitivity index-2 (ISSI-2). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Generalized estimating equations (GEE) evaluated longitudinal associations of sCD163 with insulin sensitivity, β-cell function, and incident dysglycemia adjusting for demographic and lifestyle covariates. Areas under receiver-operating-characteristic curve (AROC) tested whether sCD163 improved dysglycemia prediction in a clinical model. RESULTS Longitudinal analyses showed significant inverse associations between sCD163 and insulin sensitivity (% difference per standard deviation increase of sCD163 for HOMA2-%S (β = -7.01; 95% CI, -12.26 to -1.44) and ISI (β = -7.60; 95% CI, -11.09 to -3.97) and β-cell function (ISSI-2 (β = -4.67; 95 %CI, -8.59 to -0.58) and IGI/HOMA-IR (β = -8.75; 95% CI, -15.42 to -1.56)). Increased sCD163 was associated with greater risk for incident dysglycemia (odds ratio = 1.04; 95% CI, 1.02-1.06; P < 0.001). Adding sCD163 data to a model with clinical variables improved prediction of incident dysglycemia (AROC=0.6731 vs 0.638; P < 0.05). CONCLUSIONS sCD163 was longitudinally associated with core disorders that precede the onset of type 2 diabetes.
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Cross-Sectional and Longitudinal Examination of Insulin Sensitivity and Secretion across Puberty among Non-Hispanic Black and White Children.
Marwitz, SE, Gaines, MV, Brady, SM, Mi, SJ, Broadney, MM, Yanovski, SZ, Hubbard, VS, Yanovski, JA
Endocrinology and metabolism (Seoul, Korea). 2020;(4):847-857
Abstract
BACKGROUND Few studies using criterion measures of insulin sensitivity (SI) and insulin secretory capacity (ISC) have been conducted across puberty to adulthood. We examined how SI and ISC change from pre-puberty through adulthood. METHODS Hyperglycemic clamp studies were performed in a convenience sample of non-Hispanic Black (NHB) and White children evaluated at age 6 to 12 years and at approximately 5-year intervals into adulthood (maximum age 27 years). SI and ISC (first-phase and steady-state insulin secretion) were determined cross-sectionally in 133 unique participants across puberty and in adulthood. Additionally, longitudinal changes in SI and ISC were compared at two timepoints among three groups defined by changes in pubertal development: pre-pubertal at baseline and late-pubertal at follow-up (n=27), early-pubertal at baseline and late-pubertal at follow-up (n=27), and late-pubertal at baseline and adult at follow-up (n=24). RESULTS Cross-sectionally, SI was highest in pre-puberty and early puberty and lowest in mid-puberty (analysis of covariance [ANCOVA] P=0.001). Longitudinally, SI decreased from pre-puberty to late puberty (P<0.001), then increased somewhat from late puberty to adulthood. Cross-sectionally, first-phase and steady-state ISC increased during puberty and decreased in adulthood (ANCOVA P<0.02). Longitudinally, steady-state and first-phase ISC increased from pre-puberty to late puberty (P<0.007), and steady-state ISC decreased from late puberty to adulthood. The NHB group had lower SI (P=0.003) and greater first-phase and steady-state ISC (P≤0.001), independent of pubertal development. CONCLUSION This study confirms that SI decreases and ISC increases transiently during puberty and shows that these changes largely resolve in adulthood.
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Clinical Features of Type B Insulin Resistance in Japanese Patients: Case Report and Survey-Based Case Series Study.
Hirota, Y, Suwanai, H, Yamauchi, T, Kadowaki, T
Journal of diabetes research. 2020;:4359787
Abstract
Type B insulin resistance (TBIR) is an extremely rare disease characterized by marked hyperglycemia and insulin resistance and often coexists with autoimmune diseases. The characteristics, symptoms, blood glucose patterns, comorbidities, and treatments of TBIR all vary and are not defined. In this study, we described a case of TBIR that developed 6 months after DPP-4 inhibitor administration and immediately after the patient caught a cold. Treatment using prednisolone and insulin-like growth factor-1 was effective. We also conducted an observational survey-based case series study in a Japanese cohort comprising 21 cases. The average age of onset of TBIR was 62.3 ± 14.8 (17-84) years, and 61.9% of subjects were male. The majority of patients (90.4%) were 50 years old and over. During the study period, there was a high percentage (85.7%) of episodes of hypoglycemia, which was the trigger for diagnosis in more than 50% of cases. Glycemic patterns included 7 cases of hyperglycemia (33.3%), 10 cases of hypoglycemia (47.6%), and 4 cases of both hyperglycemia and hypoglycemia (19.1%). In the hypoglycemic group, 90.0% of patients were male. Furthermore, 71.4% of cases were antinuclear antibody positive, and 81.0% of cases were complicated with autoimmune disease. Systemic lupus erythematosus (38.1%) and Sjögren's syndrome (23.8%) were relatively common as coexisting autoimmune diseases. Treatment was based on prednisolone use, which was used in 88.9% of patients. On the other hand, the effect of IGF-1 was limited. Overall, the prognosis of TBIR was good.
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Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese nonalcoholic fatty liver disease.
Kim, D, Kim, W, Joo, SK, Kim, JH, Harrison, SA, Younossi, ZM, Ahmed, A
Liver international : official journal of the International Association for the Study of the Liver. 2019;(2):332-341
Abstract
AIMS: We compared (a) demographic and clinical characteristics and (b) determinants of nonalcoholic steatohepatitis and significant fibrosis in non-obese and obese nonalcoholic fatty liver disease. METHODS A cross-sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy-proven nonalcoholic fatty liver disease and controls was conducted. Subjects were divided by their body mass index into obese (body mass index ≥25 kg/m2 ) and non-obese (body mass index <25 kg/m2 ). RESULTS Observations in subjects with non-obese nonalcoholic fatty liver disease were in between non-obese controls and subjects with obese nonalcoholic fatty liver disease for body mass index, sagittal abdominal diameter, aminotransferase levels, insulin resistance and abdominal visceral adipose tissue area. There was no significant difference in histology between non-obese and obese subjects with nonalcoholic fatty liver disease except for lower grade of hepatic steatosis in nonobese nonalcoholic fatty liver disease and higher severity of hepatic fibrosis in nonobese nonalcoholic steatohepatitis. Predictors of nonalcoholic steatohepatitis in nonobese subjects included females (odds ratio 2.49), higher alanine aminotransferase (odds ratio 1.03), lower high-density lipoprotein cholesterol (odds ratio 0.96), higher prevalence of diabetes (odds ratio 3.65) and higher visceral adipose tissue area (odds ratio 1.63 per standard deviation increase of visceral adipose tissue area) while age (odds ratio 1.04), higher aspartate aminotransferase (odds ratio 1.02), diabetes (odds ratio 2.76) and higher visceral adipose tissue area (odds ratio 1.57 per standard deviation increase) were associated with significant fibrosis in the non-obese. Sagittal abdominal diameter was independently associated with nonalcoholic steatohepatitis or significant fibrosis among subjects with non-obese nonalcoholic fatty liver disease. CONCLUSION While there were a few phenotypic differences from obese subjects, non-obese subjects with nonalcoholic fatty liver disease displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non-obese nonalcoholic fatty liver disease advances to more severe disease.