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Journal of the National Cancer Institute Mar 2023Although unopposed estrogen exposure is considered a major driver of endometrial carcinogenesis, chronic inflammation and insulin resistance and hyperinsulinemia are...
BACKGROUND
Although unopposed estrogen exposure is considered a major driver of endometrial carcinogenesis, chronic inflammation and insulin resistance and hyperinsulinemia are also major endometrial cancer risk factors. However, it is unclear whether diets with inflammatory or insulinemic potential are associated with risk of endometrial cancer.
METHODS
We followed 48 330 women from the Nurses' Health Study (1984-2016) and 85 426 women from the Nurses' Health Study II (1989-2017). Using food frequency questionnaires, we calculated repeated measures of empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which characterize the potential of the whole diet to modulate circulating biomarkers of inflammation or C-peptide, respectively. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for type I endometrial cancer risk.
RESULTS
We documented 1462 type I endometrial cancer cases over 2 823 221 person-years of follow-up. In the pooled multivariable-adjusted analyses, women in the highest compared with lowest quintiles were at higher risk of type I endometrial cancer (EDIP HRQ5vsQ1 = 1.46, 95% CI = 1.24 to 1.73; Ptrend < .001; EDIH HRQ5vsQ1 = 1.58, 95% CI = 1.34 to 1.87; Ptrend < .001). Additional adjustment for body mass index attenuated the associations (EDIP HR = 1.03, 95% CI = 0.87 to 1.22; EDIH HR = 1.01, 95% CI = 0.85 to 1.21), and mediation analyses showed that body mass index may explain 60.4% (95% CI = 37.4% to 79.6%; P < .001) and 71.8% (95% CI = 41.0% to 90.4%; P < .001) of the association of endometrial cancer with EDIP and EDIH, respectively.
CONCLUSIONS
In this large cohort study, higher dietary inflammatory and insulinemic potential were each associated with increased endometrial cancer incidence, and this association may be almost entirely mediated by adiposity.
Topics: Female; Humans; Cohort Studies; Diet; Endometrial Neoplasms; Hyperinsulinism; Inflammation; Risk Factors; United States
PubMed: 36515492
DOI: 10.1093/jnci/djac229 -
Hormone Research 2008Hyperinsulinaemic hypoglycaemia is a cause of persistent hypoglycaemia in the neonatal and infancy periods. Prompt recognition and management of patients with... (Review)
Review
Hyperinsulinaemic hypoglycaemia is a cause of persistent hypoglycaemia in the neonatal and infancy periods. Prompt recognition and management of patients with hyperinsulinaemic hypoglycaemia are essential, if brain damage and long-term neurological sequelae are to be avoided. Hyperinsulinaemic hypoglycaemia can be transient, prolonged, or persistent (congenital). Advances in the fields of molecular biology, genetics, and pancreatic beta-cell physiology are beginning to provide novel insights into the mechanisms causing congenital forms of hyperinsulinism. So far mutations in six different genes have been described that lead to unregulated insulin secretion. The histological differentiation of focal and diffuse congenital hyperinsulinism has radically changed the surgical approach to this disease. Until recently, highly invasive investigations were performed to localize the focal lesion, but recent experience with (18)F-L-dopa positron emission tomography scanning suggests that this technique is highly sensitive for differentiating diffuse from focal disease as well as for accurately locating the focal lesion. Despite recent advances, the genetic basis of congenital hyperinsulinism is still unknown in about 50% of the patients, and the management of medically unresponsive diffuse disease remains a real challenge.
Topics: Channelopathies; Congenital Hyperinsulinism; Humans; Infant; Potassium Channels
PubMed: 18059080
DOI: 10.1159/000111789 -
Cell Cycle (Georgetown, Tex.) Nov 2013Studies in mammals have demonstrated that hyperglycemia and hyperinsulinemia are important factors in aging and cancer. Inactivation of insulin/insulin-like signaling... (Review)
Review
Studies in mammals have demonstrated that hyperglycemia and hyperinsulinemia are important factors in aging and cancer. Inactivation of insulin/insulin-like signaling increases lifespan in nematodes, fruit flies, and mice. Life-prolonging effects of caloric restriction are in part due to reduction in IGF-1, insulin, and glucose levels. Antidiabetic biguanides such as metformin, which reduce hyperglycemia and hyperinsulinemia by decreasing insulin resistance, extend lifespan, and inhibit carcinogenesis in rodents. Will antidiabetic biguanides increase lifespan in humans?
Topics: Aging; Animals; Carcinogenesis; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Longevity; Metformin
PubMed: 24189526
DOI: 10.4161/cc.26928 -
Best Practice & Research. Clinical... Dec 2013Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia in children and adults. The diagnosis of hyperinsulinemic hypoglycemia relies on the... (Review)
Review
Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia in children and adults. The diagnosis of hyperinsulinemic hypoglycemia relies on the evaluation of the biochemical profile at the time of hypoglycemia, however, contrary to common perception, plasma insulin is not always elevated. Thus, the diagnosis must often be based on the examination of other physiologic manifestations of excessive insulin secretion, such as suppression of glycogenolysis, lipolysis and ketogenesis, which can be inferred by the finding of a glycemic response to glucagon, and the suppression of plasma free fatty acids and beta-hydroxybutyrate concentrations during hypoglycemia.
Topics: Blood Glucose; Glucagon; Humans; Hyperinsulinism; Hypoglycemia; Insulin
PubMed: 24275188
DOI: 10.1016/j.beem.2013.06.005 -
Acta Medica Portuguesa 2000The western way of life favours the development of a state of insulin resistance, in genetically predisposed subjects. In this state, greater levels of insulin are... (Review)
Review
The western way of life favours the development of a state of insulin resistance, in genetically predisposed subjects. In this state, greater levels of insulin are necessary so that an answer can be obtained and, consequently, hyperinsulinism occurs. Insulin has several target tissues, thus insulin resistance is associated with the dysfunction of a multiplicity of tissues, organs and systems in the body (Syndrome X). All of those dysfunctions together with hyperinsulinism can greatly enhance the risk of atherosclerotic vascular disease. In this article we review the dysfunction at several levels, including blood pressure, endothelium, lipid metabolism and fibrinolytic system and the way they can, together with hyperinsulinism, induce atherogenesis. We review some of the therapeutic options that can reduce this state of insulin resistance as well as the morbidity and mortality associated with atherosclerosis.
Topics: Arteriosclerosis; Cholesterol, HDL; Cholesterol, VLDL; Fatty Acids; Humans; Hyperinsulinism; Hypertension; Insulin; Insulin Resistance; Obesity; Risk Factors
PubMed: 11155488
DOI: No ID Found -
Pharmacoepidemiology and Drug Safety Jan 2017Octreotide is a synthetic peptide analog of naturally occurring somatostatin. Octreotide is used off-label in children <6 years of age for hyperinsulinism,...
BACKGROUND
Octreotide is a synthetic peptide analog of naturally occurring somatostatin. Octreotide is used off-label in children <6 years of age for hyperinsulinism, chylothorax, and gastrointestinal bleeding. There is a lack of controlled data on efficacy or potential adverse events from this off-label use.
METHODS
Three pediatric hospitals participated in this study. Patients were hospitalized January 2007-December 2010 and administered octreotide for congenital hyperinsulinism (CHI) at least 1 day. Variables assessed included octreotide dosage, patient demographics, medical interventions, concomitant medicines, serious adverse events (SAEs) including necrotizing enterocolitis (NEC), and mortality.
RESULTS
The 103 patient sample had a median gestational age of 38 weeks. During the study period, two patients died: one from NEC and the other from cardiomyopathy/sepsis. There were 11 other SAEs in the 101 surviving patients.
CONCLUSION
This study highlights potential risks in administering octreotide off-label. This study, like several other published studies, has highlighted NEC in a full-term infant treated with octreotide. It is important to study the efficacy and the safety of octreotide for hyperinsulinism. In the interim, it might be prudent to prescribe octreotide in CHI neonates only in the absence of other risk factors for NEC. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Child; Child, Preschool; Enterocolitis, Necrotizing; Female; Gastrointestinal Agents; Humans; Hyperinsulinism; Infant; Infant, Newborn; Male; Octreotide; Off-Label Use; Retrospective Studies; Risk Factors
PubMed: 27910218
DOI: 10.1002/pds.4144 -
Open Veterinary Journal Jan 2020Hyperinsulinemia associated with equine metabolic syndrome and pituitary pars intermedia dysfunction is a risk factor for laminitis. Research in other species has shown...
BACKGROUND
Hyperinsulinemia associated with equine metabolic syndrome and pituitary pars intermedia dysfunction is a risk factor for laminitis. Research in other species has shown elevated body iron levels as both a predictor and consequence of insulin resistance. In humans, this is known as dysmetabolic hyperferritinemia.
AIM
To explore the relationship between equine hyperinsulinemia and body iron levels.
METHODS
We reviewed case histories and laboratory results from an open access database maintained by the Equine Cushing's and Insulin Resistance Group Inc. (ECIR). We identified 33 horses with confirmed hyperinsulinemia and laboratory results for serum iron, total iron binding capacity, and ferritin. Pearson correlation was used to test the relationship between insulin and iron indices. Additionally, we performed a secondary analysis of a previously reported controlled trial that was originally designed to test the correlation between iron status and the insulin response in horses. Here, we used a -test to compare the mean values of insulin and ferritin between horses we categorized as normal or hyperinsulinemic based on their response to an oral challenge.
RESULTS
Serum ferritin exceeded published reference range in 100% of the horses identified from the ECIR database. There were no statistically significant associations between insulin indices (RISQI, log insulin) and iron indices (log serum iron, log TSI%, log ferritin). There were trends for a negative association between RISQI and log iron [(31) = -0.33, = 0.058] and a positive association between age and ferritin [(30) = 0.34, = 0.054]. From the secondary data analysis of published data, we found significantly elevated ferritin ( = 0.05) in horses considered hyperinsulinemic by dynamic insulin testing compared to horses with a normal response.
CONCLUSION
These results suggest the potential for iron overload in hyperinsulinemic horses, a feature documented in other species and should stimulate further study into the relationship between insulin and iron dysregulation in the horse.
Topics: Animals; Female; Ferritins; Horse Diseases; Horses; Hyperinsulinism; Insulin; Iron Overload; Male
PubMed: 32042647
DOI: 10.4314/ovj.v9i4.2 -
Archives of Disease in Childhood. Fetal... Mar 2000Congenital hyperinsulinism (HI) is a clinically and genetically heterogeneous entity. The clinical heterogeneity is manifested by severity ranging from extremely severe,... (Review)
Review
Congenital hyperinsulinism (HI) is a clinically and genetically heterogeneous entity. The clinical heterogeneity is manifested by severity ranging from extremely severe, life threatening disease to very mild clinical symptoms, which may even be difficult to identify. Furthermore, clinical responsiveness to medical and surgical management is extremely variable. Recent discoveries have begun to clarify the molecular aetiology of this disease and thus the mechanisms responsible for this clinical heterogeneity are becoming more clear. Mutations in 4 different genes have been identified in patients with this clinical syndrome. Most cases are caused by mutations in either of the 2 subunits of the beta cell ATP sensitive K(+) channel (K(ATP)), whereas others are caused by mutations in the beta cell enzymes glucokinase and glutamate dehydrogenase. However, for as many as 50% of the cases, no genetic aetiology has yet been determined. The study of the genetics of this disease has provided important new information about beta cell physiology. Although the clinical ramifications of these findings are still limited, in some situations genetic studies might greatly aid in patient management.
Topics: B-Lymphocytes; Genotype; Glucokinase; Glutamate Dehydrogenase; Humans; Hyperinsulinism; Infant; Infant, Newborn; Insulin; Insulin Secretion; Mutation; Phenotype; Potassium Channels; Terminology as Topic
PubMed: 10685979
DOI: 10.1136/fn.82.2.f79 -
Frontiers in Endocrinology 2021Despite improvements in diagnosis and therapeutic advances in treatment, congenital hyperinsulinism (CHI) remains a severe disease with high patient impairment. We aimed...
INTRODUCTION
Despite improvements in diagnosis and therapeutic advances in treatment, congenital hyperinsulinism (CHI) remains a severe disease with high patient impairment. We aimed to review the literature on Health-related Quality of Life in children and adolescents with congenital hyperinsulinism and summarize the findings.
MATERIALS AND METHODS
For this scoping review, a literature search was conducted in PubMed and Web of Science in May 2021. Inclusion and exclusion criteria for the selection of articles were defined a priori.
RESULTS
Two hundred and forty-five (245) articles were identified through the search and screened on the basis of title and abstract. The full texts of forty articles were then assessed. Finally, four articles (published 2012-2020) describing Health-related Quality of Life in children and adolescents with congenital hyperinsulinism were included. The study designs were heterogeneous and included cross-sectional observational studies (n=2), clinical trials (n =1), and case reports (n=1) with different sample sizes. Three studies were conducted in European countries and one in Japan. The results for Health-related Quality of Life revealed inconsistencies.
CONCLUSION
There are only a few studies looking at Health-related Quality of Life in children and adolescents with congenital hyperinsulinism. To gain a comprehensive understanding of the impact of congenital hyperinsulinism on Health-related Quality of Life in children and adolescents, it is necessary to use both generic and condition-specific instruments to measure Health-related Quality of Life of young patients in larger samples, to collect longitudinal data, and to consider qualitative research approaches.
Topics: Adolescent; Child; Congenital Hyperinsulinism; Cross-Sectional Studies; Humans; Observational Studies as Topic; Quality of Life
PubMed: 34925243
DOI: 10.3389/fendo.2021.784932 -
Noise & Health 2020Hyperinsulinemia is the most common metabolic change associated with cochleovestibular diseases.
CONTEXT
Hyperinsulinemia is the most common metabolic change associated with cochleovestibular diseases.
AIM
We aimed to investigate the auditory functions in hyperinsulinemic individuals.
SETTINGS AND DESIGN
A total of 164 patients were included in this case-control study. While 76 patients with insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] of ≥2.5) constituted the case group, 88 patients with HOMA-IR values of <2.5 constituted the control group of the study.
MATERIAL AND METHODS
The 75 g oral glucose tolerance test, blood biochemistry tests, hormonal analysis, audiological assessment, electrocochleography (EcochG), and transient evoked otoacoustic emissions (TEOAE) testing were performed.
STATISTICAL ANALYSIS
One-way analysis of variance and Kruskal-Wallis analysis of variance were used for the comparison of the metabolic and ear parameters in the normal glucose tolerance (NGT), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT) groups. The chi-square test was used to compare nominal variables. Spearman and Pearson correlation coefficients were used for the correlation analyses of continuous variables.
RESULTS
The pure tone audiometry at 0.5, 1, 2, and 4 kHz was better in the case group than in the control group. A positive correlation was found between HbA1c and right ear 0.5, 1, 4, and 8 kHz threshold values and left ear 2, 4, 6, and 8 kHz threshold values. A negative correlation was found between HbA1c and speech discrimination scores. The right ear 1.00 and 2.83 kHz TEOAE measurements in the individuals with NGT were found higher than those in patients with IGT, and the 1.42 kHz TEOAE measurements and reproducibility were found higher than those in patients with IFG. The left ear 1.00 and 1.42 kHz TEOAE measurements of the IGT patients were found lower than those of IFG and NGT patients.
CONCLUSION
We showed that hearing was worsening in hyperinsulinemic patients and prediabetic conditions were related to hearing function impairment.
Topics: Adult; Analysis of Variance; Audiometry, Evoked Response; Audiometry, Pure-Tone; Blood Glucose; Case-Control Studies; Cochlea; Cochlear Diseases; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Otoacoustic Emissions, Spontaneous; Prospective Studies; Reproducibility of Results; Single-Blind Method; Vestibular Diseases
PubMed: 33402607
DOI: 10.4103/nah.NAH_41_20