Risk Of Glucose Metabolism Disorders Research Articles

Behind BMI: The Potential Indicative Role of Abdominal Ectopic Fat on Glucose Metabolism

Introduction: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. Methods: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. Results: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). Conclusion: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders.

DNA methylation regulates pancreatic gene expression and links maternal high-fat diet to the offspring glucose metabolism

Maternal high-fat diet (HFD) is related to an increased risk of glucose metabolism disorders throughout the whole life of offspring. The pancreas is a glucose homeostasis regulator. Accumulating evidence has revealed that maternal HFD affects offspring pancreas structure and function. However, the potential mechanism remains unclear. In this study, the mouse dam was fed with HFD or control diet (CD) during prepregnancy, pregnancy and lactation. The pancreatic insulin secretion function and islet genome methylome of offspring were analyzed. Pancreatic islet specific gene methylation was detected by using MeDIP qPCR. The results showed that body weight, blood glucose after oral glucose loads, fasting serum insulin, and HOMA-IR index values were significantly higher in male 12-week-old offspring from HFD dams than in the offspring from CD dams. Maternal HFD induced insulin secretion defects in male offspring. Compared with that in maternal CD group, methylation of the Abcc8 and Kcnj11 genes was increased in maternal HFD group in male offspring pancreatic islets. Furthermore, the expression levels of Abcc8 and Kcnj11 were downregulated by intrauterine exposure to a maternal HFD. In summary, maternal HFD results in a long-term functional disorder of the pancreas that is involved in insulin secretion-related gene DNA hypermethylation.

Former long-term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: A prospective, population-based cohort study.

Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. This was a prospective, longitudinal birth cohort study with long-term follow-up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2-h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin-only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6-9.2) but not of type 2 diabetes mellitus. Former progestin-only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol-lowering medication. Former long-term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.

Trpc5-regulated AMPKα/mTOR autophagy pathway is associated with glucose metabolism disorders in low birth weight mice under overnutrition

Previous studies have shown that low birth weight (LBW) individuals are at higher risk of glucose metabolism disorders compared with normal birth weight (NBW) individuals under overnutrition conditions, but the mechanism remains unclear. To explore the underlying mechanism of glucose metabolism disorders induced by LBW under overnutrition in adulthood, the prenatal malnutrition method was applied to ICR mice to establish the LBW mice model and high-fat diets were used to mimic overnutrition conditions. Then the mechanism was further explored on Hepg2 cells treated with nutritional deprivation plus palmitic acid. The results showed that LBW plus high-fat interventions will cause glucose metabolism disorders and inhibit autophagy flux in adulthood. Moreover, the expression of TRPC5-regulated AMPK/mTOR autophagy pathway was downregulated by LBW with high-fat interventions. Collectively, LBW plus high-fat intervention increased the risk of glucose metabolism disorders, which may be related to the alteration of TRPC5 expression level and its regulation of the AMPKα/mTOR autophagy pathway. This study may provide a fundamental basis for the molecular mechanism of glucose metabolism disorders induced by LBW with high-fat diets in adulthood and a new target for the treatment of metabolic diseases in LBW individuals.

CYP3A and CYP2B6 Genotype Predicts Glucose Metabolism Disorder among HIV Patients on Long-Term Efavirenz-Based ART: A Case-Control Study.

Long-term antiretroviral treatment (cART) increases the risk of glucose metabolism disorders (GMDs). Genetic variation in drug-metabolizing enzymes and transporters may influence susceptibility to cART-associated GMDs. We conducted a case-control study to investigate the association of pharmacogenetic variations with cART-induced GMDs. A total of 240 HIV patients on long-term efavirenz-based cART (75 GMD cases and 165 controls without GMDs) were genotyped for CYP3A4*1B, CYP3A5 (*3,*6), CYP2B6*6, UGT2B7*2, ABCB1 (c.3435C>T, c.4036A>G), and SLCO1B1 (*1b, *5). GMD cases were defined as the presence of impaired fasting glucose, insulin resistance, or diabetes mellitus (DM). Case-control genotype/haplotype association and logistic regression analysis were performed by adjusting for age, sex, and BMI. The major CYP3A haplotype were CYP3A5*3 (53.8%), CYP3A4*1B (17.3%), combinations of CYP3A4*1B, and CYP3A5*6 (10.9%), and CYP3A wild type (7%). CYP3A5*6 allele (p = 0.005) and CYP3A5*6 genotype (p = 0.01) were significantly associated with GMD cases. Multivariate analysis indicated CYP3A haplotype as a significant predictor of GMD (p = 0.02) and IFG (p = 0.004). CYP2B6*6 significantly predicted DM (p = 0.03). CYP3A haplotype and CYP2B6*6 genotype are independent significant predictors of GMD and DM, respectively, among HIV patients on long-term EFV-based cART.

Severe malnutrition or famine exposure in childhood and cardiometabolic non-communicable disease later in life: a systematic review

IntroductionChild malnutrition (undernutrition) and adult non-communicable diseases (NCDs) are major global public health problems. While convincing evidence links prenatal malnutrition with increased risk of NCDs, less is known about the...

Clinical characteristics and incidence of glucose metabolism disorders during the follow-up of surgically treated insulinomas.

Insulinomas are pancreatic endocrine tumors characterized by hypoglycemia resulting from hypersecretion of insulin. The long-term impact of surgical treatment of insulinomas, particularly the risk of glucose metabolism disorders, remains largely unknown. We retrospectively evaluated all patients with insulinoma submitted to surgery at Centro Hospitalar Universitário de São João (Porto, Portugal) between 1980 and 2016. We evaluated baseline characteristics of patients at presentation, imaging evaluation, surgical treatment, characteristics of the tumors, perioperative complications, disease remission, and long-term follow-up and metabolic outcomes. Twenty-eight patients with insulinomas submitted to surgical treatment were included. Sixty-one percent were female, and the average age was 46.4 years. The most reported symptoms were confusion (72%) and diaphoresis (56%). The most used imaging technique was abdominal CT (72%), and the test with the highest percentage of positive results was endoscopic ultrasound (80%). The most used surgical procedure was partial pancreatic resection (71%). The mean tumor diameter was 2.1 cm and 11% of the tumors had lymph node involvement at diagnosis. Pancreatic fistula was the most common postoperative acute complications (21%). After surgery, patients were followed for a median time of 80 months (25th-75th percentile: 20-148 months). Eight patients (32%) developed glucose metabolism disorders (seven developed diabetes and one prediabetes). One of these patients developed albuminuria, and no macrovascular complications were observed during the follow-up. Disorders of glucose metabolism are a frequent complication during follow-up of surgically treated insulinomas. The prevention, early diagnosis, and treatment of diabetes should be a priority in the follow-up of these patients.

No increased risk of glucose metabolism disorders in adults with growth hormone deficiency undergoing long-term treatment with biosimilar somatropin (Omnitrope\xae): data from an observational, longitudinal study

BackgroundTo evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study.MethodsPATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%.ResultsUp to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29–84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45–72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD.ConclusionsBased on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this.Trial registrationNot applicable.

Extensive metabolic remodeling after limiting mitochondrial lipid burden is consistent with an improved metabolic health profile

Mitochondrial lipid overload in skeletal muscle contributes to insulin resistance, and strategies limiting this lipid pressure improve glucose homeostasis; however, comprehensive cellular adaptations that occur in response to such an intervention have not been reported. Herein, mice with skeletal muscle-specific deletion of carnitine palmitoyltransferase 1b (Cpt1bM-/-), which limits mitochondrial lipid entry, were fed a moderate fat (25%) diet, and samples were subjected to a multimodal analysis merging transcriptomics, proteomics, and nontargeted metabolomics to characterize the coordinated multilevel cellular responses that occur when mitochondrial lipid burden is mitigated. Limiting mitochondrial fat entry predictably improves glucose homeostasis; however, remodeling of glucose metabolism pathways pales compared with adaptations in amino acid and lipid metabolism pathways, shifts in nucleotide metabolites, and biogenesis of mitochondria and peroxisomes. Despite impaired fat utilization, Cpt1bM-/- mice have increased acetyl-CoA (14-fold) and NADH (2-fold), indicating metabolic shifts yield sufficient precursors to meet energy demand; however, this does not translate to enhance energy status as Cpt1bM-/- mice have low ATP and high AMP levels, signifying energy deficit. Comparative analysis of transcriptomic data with disease-associated gene-sets not only predicted reduced risk of glucose metabolism disorders but was also consistent with lower risk for hepatic steatosis, cardiac hypertrophy, and premature death. Collectively, these results suggest induction of metabolic inefficiency under conditions of energy surfeit likely contributes to improvements in metabolic health when mitochondrial lipid burden is mitigated. Moreover, the breadth of disease states to which mechanisms induced by muscle-specific Cpt1b inhibition may mediate health benefits could be more extensive than previously predicted.

Modern approaches to diagnostics of hyperandrogenism distributed forms in reproductive aged women

Гіперандрогенія (ГА) характеризується підвищеними рівнями циркулюючих андрогенів та/або наявністю клінічних проявів їх біологічних ефектів. Частота ГА в жіночій популяції в середньому становить 8%. Підвищення рівнів андрогенів може бути зумовлене різними, не завжди відомими факторами і реалізовуватися за допомогою різних механізмів. Присутність ГА в жінок чинить негативний вплив на фертильність і обмін речовин. За походженням ГА поділяють на істинні наднирникові або яєчникові; периферичні/рецепторні; ятрогенні; транспортні; вторинні. ГА супроводжує досить широкий спектр захворювань і станів. Більшість захворювань супроводжуються змішаними формами ГА, коли є основне джерело і додаткові або вторинні. Внесок тих чи інших джерел ГА при змішаних формах може змінюватися з плином часу і в залежності від впливу екзогенних або ендогенних факторів. Часто важливою складовою ГА є переважання вільної форми тестостерону за рахунок зниженого синтезу глобуліну, що зв’язує статеві стероїди. Все це диктує необхідність диференційованого підходу до лабораторної діагностики ГА при різних захворюваннях, особливо при порушенні жіночої фертильності. До поширених ГА, що впливають на жіночу фертильність і пов’язані з підвищеними пожиттєвими метаболічними ризиками, належать: синдром полікістозних яєчників (СПКЯ), некласичні форми вродженої гіперплазії кори наднирників (є першою патологією для диференціальної діагностики при обстеженні пацієнтки з підозрою на СПКЯ), стани, що супроводжуються оліго-/ановуляцією і вторинною ГА (гіперпролактинемія, гіперкортицизм, гіпотиреоз тощо). На сьогоднішній день рекомендовано користуватися наступним визначенням СПКЯ, що полягає у поєднанні щонайменше двох із трьох критеріїв – оліго-/ановуляція; полікістозний морфотип яєчників; клінічна та/або біохімічна ГА. Лабораторна діагностика СПКЯ включає: дослідження для виключення інших причин ГА та оліго-/ановуляції (диференціальна діагностика СПКЯ); дослідження для підтвердження діагнозу СПКЯ відповідно до критеріїв (визначення біохімічної ГА); додаткові дослідження для діагностики СПКЯ, особливо нормоандрогенних форм; дослідження для діагностики метаболічних ускладнень СПКЯ.

The utilization and challenges of Japan's MID-NET® medical information database network in postmarketing drug safety assessments: A summary of pilot pharmacoepidemiological studies.

To examine the potential role of Medical Information Database Network (MID-NET® ), a newly established Japanese medical information database network, in postmarketing drug safety assessments through the characterization of its advantages and limitations in five pilot studies. The pilot studies were designed to address three major objectives in postmarketing drug safety assessments, ie, the examination of actual drug utilization, the impact of safety-related regulatory actions, and drug-associated risks. The five studies were conducted on the following topics: (a) utilization of codeine-containing products and its relationship with respiratory depression, (b) impact of a Dear Healthcare Professional letter on hypocalcemia incidence associated with denosumab (Ranmark® ) use, (c) risk of acute myocardial infarction associated with antidiabetic drug use, (d) risk of glucose metabolism disorders associated with atypical antipsychotic drug use, and (e) prospective monitoring of abnormal laboratory test results during new drug prescriptions. The pilot studies were successfully conducted and demonstrated the value of MID-NET® in postmarketing drug safety assessments. In particular, the ability to utilize laboratory test results as objective clinical indicators is a major advantage of this database. Potential limitations include a relatively small sample size and a lack of patient-level data linkages among hospitals. MID-NET® was confirmed to be a valuable database for postmarketing drug safety assessments. The use of laboratory test results to define clinical outcomes may allow more objective and accurate analyses to be conducted. These studies furthered our understanding of the characteristics of MID-NET® , including its advantages and limitations.

[The impact of obstructive sleep apnea hypopnea syndrome on glucose metabolism].

To study the influence of obstructive sleep apnea hypopnea syndrome (OSAHS) on glucose metabolism and comprehensively analyze its related factors. A total of 180 snoring patients were recruited in Sleep Disorder Center of Nanfang Hospital of Southern Medical University between January 2010 to June 2011. There were 140 patients with OSAHS and 40 subjects without OSAHS. All patients underwent both a full polysomnography (PSG) and plasma glucose measure, including fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). The FPG, 1-hour post-challenge glucose (1 hPG) and 2-hour post-challenge glucose (2 hPG) were respectively compared in patients with different apnea hypopnea index (AHI), the lowest saturation of pulse oximetry (SpO₂) and sleep architecture. The incidence of glucose metabolism disorders was higher in patients with OSAHS than that of those without (diabetes: 21.4% vs 5.0%; prediabetes: 34.3% vs 25.0%). The FPG, 1 hPG and 2 hPG in patients with different AHI was significantly different respectively (all P < 0.01), so as in patients with different lowest oxygen saturation (all P < 0.01). Post-load glucose levels of patients with different AHI were still significantly different after adjustment for neck circumference (1 hPG: P = 0.004; 2 hPG: P = 0.048). FPG, 1 hPG and 2 hPG were associated with AHI (r = 0.167, 0.277, 0.196, all P < 0.05), mean SpO₂(r = -0.154, -0.214, -0.182, all P < 0.05) and the lowest SpO₂(r = -0.224, -0.231, -0.159, all P < 0.05); While FPG, 1 hPG and 2 hPG were not significantly associated with N1 + N2, N3 and rapid eye movement (REM) sleeps (all P > 0.05). The risk of glucose metabolism disorders increased with the severity of OSAHS. Compared with fasting glucose, post-load glucose was more affected by OSAHS independent of obesity. Compared with sleep architecture or sleep efficiency, glucose metabolism disorders seem to be associated with hypoxia caused by OSAHS.

A preliminary investigation of EZSCAN™ screening for impaired glucose tolerance and diabetes in a patient population.

EZSCAN™ is a non-invasive technology that evaluates sweat gland dysfunction using electrochemical skin conductance measurements, providing an opportunity to determine the risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). This study was conducted with the aims of detecting IGT and DM and investigating the efficacy and cut-off points of the EZSCAN test in a patient population. The traditional serum and plasma glucose tests were used as comparators. In this cross-sectional study, 270 previously undiagnosed patients (180 women and 90 men) with a high risk of glucose metabolism disorders (≥45 years old) were enrolled. All patients underwent an oral glucose tolerance test (OGTT) and hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and EZSCAN tests. Forty (14.8%) patients had newly diagnosed DM (NDM), 79 (29.3%) had IGT and 151 (55.9%) had normal glucose tolerance. The EZSCAN values of these groups were 48±11, 47±11 and 34±13%, respectively. For all patients, the correlation coefficient of EZSCAN was 0.462 with the OGTT (P<0.001), 0.182 with the FPG test (P<0.001) and 0.379 with the HbA1c test (P<0.001). The EZSCAN cut-off point for the detection of IGT was 37% [sensitivity, 82%; specificity, 62%; area under the curve (AUC), 0.778], and the cut-off point for NDM was 50% (sensitivity, 53%; specificity, 59%; AUC, 0.528). This study demonstrated that the non-invasive EZSCAN system is an effective screening tool for the detection of glucose dysfunction in the population tested, and that its performance in detecting previously undiagnosed IGT is superior to its performance in detecting DM.

Elevated white blood cell count is associated with higher risk of glucose metabolism disorders in middle-aged and elderly Chinese people.

White blood cell (WBC) count has been associated with diabetic risk, but whether the correlation is independent of other risk factors has hardly been studied. Moreover, very few such studies with large sample sizes have been conducted in Chinese. Therefore, we investigated the relationship between WBC count and glucose metabolism in china. We also examined the relevant variables of WBC count. A total of 9,697 subjects (mean age, 58.0 ± 9.1 years) were recruited. The subjects were classified into four groups, including subjects with normal glucose tolerance, isolated impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). We found that WBC count increased as glucose metabolism disorders exacerbated. WBC count was also positively correlated with waist hip ratio, body mass index, smoking, triglycerides, glycosylated haemoglobin A1c (HbA1c) and 2-h postprandial glucose. In addition, high density lipoprotein and the female gender were inversely correlated with WBC levels. In patients with previously diagnosed T2DM, the course of T2DM was not correlated with WBC count. Our findings indicate that elevated WBC count is independently associated with worsening of glucose metabolism in middle-aged and elderly Chinese. In addition, loss of weight, smoking cessation, lipid-modifying therapies, and control of postprandial plasma glucose and HbA1c may ameliorate the chronic low-grade inflammation.

[Association of the calpain-10 gene polymorphism with glucose metabolism disorder in pregnant women].

To study three single nucleotide polymorphisms (SNP), SNP-43, -19 and -63 of calpain-10 (CAPN10) gene in pregnant women with glucose metabolism disorders and their relationship with the risk of these disorders. Totally, 270 pregnant women including 156 with an abnormal oral glucose tolerance test (study group) and 114 healthy controls were selected among those delivered at the Department of Obstetrics and Gynecology, Peking University First Hospital from Jan. 2005 to Dec. 2006. The SNP of CAPN10 gene at positions 43, 19, and 63 were analyzed by primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR). (1) The frequencies CAPN10 SNP-19 2R/2R genotype (26.9%, 42/156) and 2R allele (48.9%, 152/312) were higher than those in controls (12.3%, 14/114 and 36.8%, 84/228, respectively; P=0.012, 0.006). (2) Stratified analysis according to family history of diabetes mellitus showed the proportion of the CAPN10 SNP-19 2R/2R+2R/3R genotypes (83%, 47/57) in the study group were significantly higher than that of control group (52%, 11/21; P=0.009), and the proportion of SNP-63 T/T+T/C genotypes (47%, 27/57) in study group were significantly higher than that of control group (14%, 3/21; P=0.026) among those with positive family history. (3) The combined effect of CAPN10 SNP-43, -19 and -63 on glucose metabolism disorders was analyzed by comparing with the other haplotypes and showed that the haplotype 121 distribution in study group was significantly higher than those in controls (P=0.036), and 221 haplotype was significantly lower than controls (P=0.042). (1) CAPN10 SNP-19 is associated with glucose metabolism disorders in pregnant women. And 2R allele might be the risk factor. CAPN10 SNP-19 2R/2R+2R/3R and SNP-63 T/T+T/C genotypes might increase the risk of glucose metabolism disorders in women with positive family history. Haplotype 121 might increase the risk of glucose metabolism disorders in pregnant women and 221 be a protective factor.