Homeostatic Model Assessment-estimated Insulin Resistance Research Articles

White blood cells and type 2 diabetes: A Mendelian randomization study.

Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits. The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits. Using the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified. WBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding.

Prevalence of risk factors for diabetes in adult offspring of type 2 diabetes mellitus patients

Background: The risk of developing type 2 diabetes mellitus (T2DM) and associated metabolic abnormalities is higher in adult offspring of patients with T2DM. Various genetic and environmental influences play a facilitatory role. These determinants can lead to the early onset of hyperglycemia, unrecognized end-organ changes, and cardiovascular morbidity. Objective: The objective of this study was to identify the presence of undiagnosed diabetes and prediabetes in the otherwise healthy adult offspring of patients with T2DM and to study early metabolic abnormalities among these individuals. Materials and Methods: The study population consisted of 100 healthy offspring aged 18 years and above, of parents with T2DM, enrolled from the medicine outpatient area. Anthropometric characteristics, routine investigations and diabetes defining parameters, fasting plasma insulin, and homeostatic model assessment-estimated insulin resistance (HOMA-IR) were assessed. Results: The age and body mass index of participants were 32.30 ± 9.33 years and 25.08 ± 4.58 kg/m2, respectively. About 33.3% of males and 76.4% of females had abnormal waist circumference and metabolic syndrome was found in 26% of the offspring. Twenty-eight participants displayed dysglycemia, of which 10 were diagnosed with prediabetes and 18 with diabetes. C-reactive protein, total cholesterol, triglyceride values, apolipoprotein A, B, and their ratio, and HOMA-IR were significantly raised, and high-density lipoprotein was found significantly low in patients with this newly diagnosed T2DM. Conclusion: A significant number of asymptomatic offspring of patients with T2DM have incipient diabetes and prediabetes status, which is unidentified. Further, metabolic parameters are more deranged in those with newly diagnosed diabetes and prediabetes. Therefore, opportunistic screening for these offspring should be done routinely.

Correlation between Glycation-Related Biomarkers and Quality of Life in the General Japanese Population: The Iwaki Cross-Sectional Research Study.

The correlation between diabetes-related biomarkers and quality of life (QOL) remains unclear. In this cross-sectional study, we investigated the correlation between diabetes-related biomarkers and QOL in a general Japanese population who underwent health checkups as a part of the Iwaki Health Promotion Project. Male and female participants aged ≥ 20 years from Iwaki District, Hirosaki City, Aomori Prefecture who participated in the 2019 medical evaluation were recruited. QOL was evaluated using the Short Form Health Survey 36 (SF-36). Fasting blood glucose, homeostatic model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), glycoalbumin, and plasma pentosidine were also evaluated as diabetes-related markers. Of the 1065 recruited participants, 1053 completed the clinical and QOL evaluations. Multivariate regression analysis revealed that upregulated diabetes-related markers levels were correlated with decreased SF-36 scores. Blood glucose, HOMA-IR, HbA1c, glycoalbumin, and plasma pentosidine levels were correlated with general health. Moreover, plasma pentosidine levels were correlated with role physical, social functioning, and role emotional in addition to general health. These results indicated that the levels of diabetes-related biomarkers, particularly the levels of plasma pentosidine, a glycation marker, were associated with QOL in our cohort.

Use of a K-nearest neighbors model to predict the development of type 2 diabetes within 2 years in an obese, hypertensive population

Prediabetes is a type of hyperglycemia in which patients have blood glucose levels above normal but below the threshold for type 2 diabetes mellitus (T2DM). Prediabetic patients are considered to be at high risk for developing T2DM, but not all will eventually do so. Because it is difficult to identify which patients have an increased risk of developing T2DM, we developed a model of several clinical and laboratory features to predict the development of T2DM within a 2-year period. We used a supervised machine learning algorithm to identify at-risk patients from among 1647 obese, hypertensive patients. The study period began in 2005 and ended in 2018. We constrained data up to 2 years before the development of T2DM. Then, using a time series analysis with the features of every patient, we calculated one linear regression line and one slope per feature. Features were then included in a K-nearest neighbors classification model. Feature importance was assessed using the random forest algorithm. The K-nearest neighbors model accurately classified patients in 96% of cases, with a sensitivity of 99%, specificity of 78%, positive predictive value of 96%, and negative predictive value of 94%. The random forest algorithm selected the homeostatic model assessment-estimated insulin resistance, insulin levels, and body mass index as the most important factors, which in combination with KNN had an accuracy of 99% with a sensitivity of 99% and specificity of 97%. We built a prognostic model that accurately identified obese, hypertensive patients at risk for developing T2DM within a 2-year period. Clinicians may use machine learning approaches to better assess risk for T2DM and better manage hypertensive patients. Machine learning algorithms may help health care providers make more informed decisions.

Daily watermelon consumption decreases plasma sVCAM-1 levels in overweight and obese postmenopausal women

Postmenopausal status is associated with an increase in total and abdominal body fat as well as increased incidence of insulin resistance and cardiovascular disease. The purpose of this study was to determine if watermelon supplementation affects select systemic markers of atherosclerosis and measures of insulin resistance in overweight and obese postmenopausal women. We hypothesized that overweight and obese postmenopausal women consuming 100% watermelon puree daily for 6 weeks would have improved levels of select systemic markers connected with cardiovascular disease without changing markers of insulin resistance. To test this hypothesis, overweight and obese postmenopausal women were recruited to participate in this study. Participants were randomly assigned to either the control group (no intervention) or the watermelon puree group (WM) for 6 weeks. Plasma concentration of markers connected with atherosclerosis and glycemic control were measured pre- and poststudy. A significant 6% decrease in soluble vascular cell adhesion molecule-1 occurred pre- to poststudy in WM, P = .003. The pattern of change in fasting blood glucose (P = .633), insulin (P = .158), and homeostatic model assessment–estimated insulin resistance (P = .174) did not differ between groups. Pre- to poststudy increases were measured in the fasting plasma concentration of l-arginine (8%, P = .005), cis-lycopene (32%, P = .003), and trans-lycopene (42%, P = .003) in WM. We conclude that 6 weeks of watermelon supplementation improved soluble vascular cell adhesion molecule-1 levels, a marker connected to atherogenesis, independent of changes in body composition or glycemic control.

Correlation between insulin resistance and liver histology in patients with nonalcoholic steatohepatitis with and without obesity.

Insulin resistance (IR) plays a central role in pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to correlate histopathological grading and IR in overweight/obese patients with NASH as compared with lean NASH. Patients with NASH who underwent liver biopsy between January 2012 and December 2012 were included. Anthropometric, clinical, and biochemical features, necro-inflammatory grades, and fibrosis stage on liver biopsies were scored according to Brunt and non-alcoholic fatty liver disease (NAFLD) activity score (NAS). Of 42 patients, 33 (78.6%) had body mass index (BMI) ≥ 23kg/m2 (overweight/obese) while 9 had BMI < 23kg/m2 (lean). Mean fasting blood sugar (FBS) and HbA1c levels in overweight/obese patients with NASH were higher than in lean NASH (p < 0.05). The median homeostatic model assessment-estimated insulin resistance (HOMA-IR) among NASH patients with BMI ≥ 23kg/m2 was higher than among those with BMI < 23kg/m2 (3.02 [0.34-17.22] vs. 2 [0.52-5.26]; p = 0.045). However, fasting insulin levels were comparable among lean and overweight/obese patients with NASH. Metabolic syndrome could be predicted with 75% sensitivity and 85.3% specificity at a HOMA-IR cutoff value of 3.9. No significant difference was observed with regard to HOMA-IR levels with Brunt grades, Brunt staging, Brunt grades 1 and 2, Brunt scores < 2 and > 2, and NAS scores, and NAS scores < 4 and > 4. Although IR was significantly higher in overweight/obese patients with NASH as compared with that in lean patients with NASH, there was no difference in the correlation of HOMA-IR with histology between these groups.

A Double-blind Randomized Controlled Trial of Curcumin for Improvement in Glycemic Status, Lipid Profile and Systemic Inflammation in β-Thalassemia Major

Background and aimβ-Thalassemia major, the commonest inherited anemia worldwide is associated with abnormalities in glucose homeostasis and serum lipids and chronic inflammation. The aim of this study was to evaluate the effects of curcumin on glycemic status, lipid profile and high sensitive C-reactive protein (hs-CRP) levels in these patients. MethodsSixty-eight β-thalassemia major patients were recruited in this double-blind randomized controlled clinical trial. Subjects in curcumin group received two 500 mg curcumin capsules daily and the matched patients in placebo group took two placebo capsules every day for 12 weeks. Dietary intakes and biochemical parameters including hemoglobin, serum iron, fasting blood glucose (FBG), insulin, homeostatic model assessment-estimated insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), hs-CRP and lipid ratios were assessed at baseline and the end of the trial. ResultsCurcumin significantly reduced HOMA-IR (p = 0.048), TG (p = 0.020), TG/HDL-C ratio (p = 0.024) and hs-CRP levels (p = 0.022) at the end of the trial when compared with baseline values. Based on analysis of covariance, levels of TG, hs-CRP and TG/HDL ratio also decreased significantly in the curcumin group compared with the placebo group by the end of the intervention (p = 0.038, p = 0.004 and p = 0.023, respectively). Changes in other variables were not significant. ConclusionsCurcumin improved insulin resistance, lipid profile and systemic inflammation by reducing HOMA-IR, TG, TG/HDL ratio and hs-CRP levels in β-thalassemia major patients. Curcumin may be useful as an adjuvant therapy for attenuation of the metabolic complications in these patients.

Relationship among obesity, blood lipids and insulin resistance in Bangladeshi adults

IntroductionInsulin resistance (IR) and abnormal lipid profiles are the risk factors for cardiovascular diseases in obesity. To clarify the relationship of the changes in insulin resistance, body weight and lipid profile, the present study was performed on Bangladeshi adults, total of 1500 individuals at the time of their general health examination in the hospital. MethodsAfter exclusion of other endocrine diseases, the remaining 772 patients were classified as IR ≥ 2 and IR < 2 based on the homeostatic model assessment-estimated insulin resistance (HOMA-IR) index. The endocrine disease free subjects were further clustered based on age, gender and obesity. The anthropometric and biochemical profiles were statistically analyzed and correlated with IR ≥ 2 and IR<2 groups as well as other clusters of the subjects. Apart from some disparities, notable differences were observed in all anthropometric data. ResultsTotal cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and serum insulin levels were significantly higher in IR ≥ 2 group in comparison with IR<2 group. Obesity and dyslipidemia were associated as prevalent components of IR. Generalized linear model revealed that TC: LDL and TG: HDL had significant effect on IR. Age group II (41–60 years old) subjects had significantly higher lipid profile compared to age group I (20–40 years old) and age group III (61–80 years old). ConclusionsResults reported herein support the notion that lipoprotein ratios might be the reliable biomarkers to evaluate IR.

Does Nox2 Overactivate in Children with Nonalcoholic Fatty Liver Disease?

It is unknown whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2) activation is early associated with endotoxemia and liver damage in nonalcoholic fatty liver disease (NAFLD). To address this issue, we evaluated Nox2 activation, oxidative stress, gut permeability, and lipopolysaccharide (LPS) serum levels in 67 children with biopsy-proven NAFLD and 73 controls. Compared with controls, NAFLD patients had higher Nox2 activity, isoprostane, zonulin, and LPS levels. Multivariate linear regression analysis showed that triglycerides, high-density lipoprotein (HDL), homeostatic model assessment-estimated insulin resistance (HOMA-IR), LPS, and isoprostanes were independently associated with Nox2-derivative peptide (sNox2-dp) levels. Within the NAFLD group, patients with nonalcoholic steatohepatitis (NASH) had significant higher levels of sNox2-dp, isoprostanes, LPS, triglycerides, HOMA-IR, fasting glucose and insulin, and lower HDL than those without NASH. Furthermore, sNox2-dp levels were linearly associated with the histological grading of steatosis, inflammation, ballooning, fibrosis, and NAFLD activity score. This study provides evidence that children with NAFLD have Nox2 overactivation compared with controls and significant association with the degree of liver damage. The close relationship between Nox2 and LPS serum levels leads to hypothesize a potential role for gut-derived LPS in eliciting systemic Nox2 activation.

The relationship of maternal glycemia to childhood obesity and metabolic dysfunction‡

Objective: To determine the association of maternal glycemia with childhood obesity and metabolic dysfunction.Study design: Secondary analysis of follow-up data 5–10 years after a mild gestational diabetes mellitus (GDM) treatment trial. The relationship between maternal oral glucose tolerance testing (OGTT) at 24–31-week gestation and body mass index (BMI), fasting glucose, insulin, and anthropometric measurements (sum of skinfolds, subscapular/triceps ratio, and waist circumference) in the offspring of untreated mild GDM and non-GDM (abnormal 50-g screen/normal OGTT) women was assessed. Multivariable regression modeling controlling for maternal and neonatal characteristics was employed.Results: A cohort of 236 untreated mild GDM and 480 non-GDM offspring were analyzed. In the combined cohort, significant correlations existed between fasting, 1, 2, and 3 h maternal glucose and subscapular/triceps ratio (all p < .04) and in all OGTT values other than the 2-hour value for homeostatic model assessment-estimated insulin resistance (HOMA-IR) (all p < .04) and sum of skinfold measurements (all p < .03). No correlation was found between OGTT values and childhood BMI Z-score. Multivariable regression modeling showed that OGTT values were associated with only sum of skinfolds and subscapular/triceps ratio and not with childhood BMI Z-score. Hispanic ethnicity and prepregnancy maternal BMI were most consistently related to childhood BMI Z-score and HOMA-IR, and Hispanic ethnicity with fasting glucose.Conclusions: Among women with untreated mild GDM and those without GDM, maternal glycemia is associated with childhood anthropometric measures of obesity but not childhood BMI, fasting glucose, or insulin resistance. Hispanic ethnicity, maternal BMI, and gestational weight gain were consistently related to childhood BMI.

Relationship among Obesity, Blood Lipids and Insulin Resistance in Bangladeshi Adults

Introduction: Insulin resistance (IR) and abnormal lipid profiles are the risk factors for cardiovascular diseases in obesity. To clarify the relationship of the changes in insulin resistance, body weight and lipid profile, the present study was performed on Bangladeshi adults, total of 1500 individuals at the time of their general health examination in the hospital.Methods: After exclusion of other endocrine diseases, the remaining 772 patients were classified as IR ≥ 2 and IR<2 based on the homeostatic model assessment-estimated insulin resistance (HOMA-IR) index. The endocrine disease free subjects were further clustered based on age, gender and obesity. The anthropometric and biochemical profiles were statistically analyzed and correlated with IR ≥ 2 and IR˂2 groups as well as other clusters of the subjects. Apart from some disparities, notable differences were observed in all anthropometric data.Results: Total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and serum insulin levels were significantly higher in IR ≥ 2 group in comparison with IR˂2 group. Obesity and dyslipidemia were associated as prevalent components of IR. Generalized linear model revealed that TC: LDL and TG: HDL had significant effect on IR. Age group II (41-60 years old) subjects had significantly higher lipid profile compared to age group I (20-40 years old) and age group III (61-80 years old).Conclusions: Results reported herein support the notion that lipoprotein ratios might be the reliable biomarkers to evaluate IR.

Shrimp oil extracted from the shrimp processing waste reduces the development of insulin resistance and metabolic phenotypes in diet-induced obese rats.

Diet-induced obesity, insulin resistance, impaired glucose tolerance, chronic inflammation, and oxidative stress represent the main features of type 2 diabetes mellitus. The present study was conducted to examine the efficacy and mechanisms of shrimp oil on glucose homeostasis in obese rats. Male CD rats fed a high-fat diet (52 kcal% fat) and 20% fructose drinking water were divided into 4 groups and treated with the dietary replacement of 0%, 10%, 15%, or 20% of lard with shrimp oil for 10 weeks. Age-matched rats fed a low-fat diet (10 kcal% fat) were used as the normal control. Rats on the high-fat diet showed impaired (p < 0.05) glucose tolerance and insulin resistance compared with rats fed the low-fat diet. Shrimp oil improved (p < 0.05) oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index; decreased serum insulin, leptin, hemoglobin A1c, and free fatty acids; and increased adiponectin. Shrimp oil also increased (p < 0.05) antioxidant capacity and reduced oxidative stress and chronic inflammation. The results demonstrated that shrimp oil dose-dependently improved glycemic control in obese rats through multiple mechanisms.

Relationship Between Parathormone and Obesity-Linked Disorders.

In this study, we aimed to investigate whether high parathormone (PTH) levels in obese patients contribute to the metabolic complications of obesity. A total of 400 obese subjects aged 18-65 years were included. Anthropometric bioelectrical bioimpedance measures, blood tests, and 75 gram oral glucose tolerance test results were evaluated. Of the 400 obese subjects, 335 were female. The mean age was 39 ± 10 years. The median body mass index was 36 (interquartile range 34-41). Subjects were divided into quartiles according to blood PTH levels. Groups included quartile 1 [n = 100, median PTH; 42 (range 36-45)], quartile 2 [n = 100, median PTH; 55 (51-59)], quartile 3 [n = 100, median PTH; 73 (68-78)], and quartile 4 [n = 100, median PTH; 99 (89-125)]. Quartiles were evaluated with a generalized linear model adjusted for age, sex, and season of recruitment. Systolic and diastolic blood pressure, fasting glucose, homeostatic model assessment-estimated insulin resistance, insulin sensitivity index, triglyceride level, and high-density lipoprotein cholesterol (HDL-C) were not different among quartiles. PTH and 25 hydroxyvitamin D (25(OH)D) were not associated with higher odds of prevalent metabolic syndrome in obese subjects (odds ratio, OR, 0.99 [95% confidence interval, CI, 0.981.00], P = 0.38 and 0.99 95% CI 0.96-1.01], P = 0.46, respectively). Decreased 25(OH)D levels were significantly correlated with higher odds of low HDL-C (OR 0.96 [95% CI 0.93-0.99], P = 0.04). PTH does not contribute to the occurrence of metabolic components of obesity, but there is a positive correlation between 25(OH)D and HDL-C.

CTRP1 protects against diet-induced hyperglycemia by enhancing glycolysis and fatty acid oxidation

Complement-C1q/tumor necrosis factor-α related protein 1 (CTRP1) is a 35-kDa glycoprotein that is secreted from various tissues. Although CTRP1 is highly increased in patients with type II diabetes and obesity, the metabolic roles of CTRP1 remain largely unknown. To unveil the physiological roles of CTRP1 in vivo, CTRP1 transgenic (TG) mice were challenged by a high-fat diet (HFD) and a high-sucrose drink (HS). Homeostatic model assessment-estimated insulin resistance values were decreased in HFD- or HS-fed CTRP1 TG mice compared with wild-type control mice. In this context, CTRP1 stimulated glucose uptake through the glucose transporter GLUT4 translocation to the plasma membrane and also increased glucose consumption by stimulating glycolysis. To analyze the roles of CTRP1 in lipid metabolism, acetyl-CoA carboxylase (ACC) and hormone-sensitive lipase levels were determined in CTRP1 TG mice, and the effect of CTRP1 on fatty acid oxidation was assessed in C2C12 myotubes. CTRP1 was found to inhibit ACC by phosphorylation and to stimulate fatty acid oxidation in C2C12 myotubes. Taken together, CTRP1 performs active catabolic roles in vivo. Therefore, CTRP1 seems to perform a defensive function against nutritional challenges.

Flaxseed lignan secoisolariciresinol diglucoside improves insulin sensitivity through upregulation of GLUT4 expression in diet-induced obese mice

The efficacy and mechanism of flaxseed lignan secoisolariciresinol diglucoside (SDG) on glucose hemostasis in obese mice were examined. Male C57BL/6J mice fed on a high-fat diet (60 kcal% fat) for 15 weeks were divided into four groups and treated by oral gavage with 0, 10, 100, or 1000 mg/kg/d of SDG dissolved in water for 6 weeks. Age-matched mice fed with a low-fat diet (10% kcal fat) were used as the normal control. SDG lowered fasting blood glucose, insulin, and free fatty acid levels and improved oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index in mice fed the high-fat diet. Flaxseed SDG also increased GLUT4 expression and tended to increase phosphorylated AKT to total AKT ratio in the muscle tissue. The data demonstrated that flaxseed SDG improved glycaemic control, at least in part, by enhancing insulin signalling and sensitivity in diet-induced obese mice.

Association between family history risk categories and prevalence of diabetes in Chinese population.

AimTo investigate the association between different family history risk categories and prevalence of diabetes in the Chinese population.MethodsThe family history of diabetes was obtained from each subject, and an oral glucose tolerance test was performed for measuring the fasting and postload glucose and insulin levels based on a national representative cross-sectional survey of 46,239 individuals (age ≥ 20 years) in the 2007–2008 China National Diabetes and Metabolism Disorders Study. The family history risk categories of diabetes were high, moderate, and average (FH2 and FH1: at least two generations and one generation of first-degree relatives with diabetes, respectively; FH0: no first-degree relatives with diabetes).ResultsThe age- and gender-adjusted prevalence rates of diabetes were 32.7% (95% confidence interval (CI): 26.4–39.7%) in FH2, 20.1% (95% CI: 18.2–22.1%) in FH1, and 8.4% (95% CI: 7.9–8.9%) in FH0 (P < 0.0001). The calculated homeostatic model assessment-estimated insulin resistance (HOMA-IR), Matsuda insulin sensitivity index (ISI), and insulinogenic index (ΔI30/ΔG30) values showed significant trending changes among the three risk categories, with the most negative effects in FH2. Multivariate logistic regression analysis showed that the odds ratios of having diabetes were 6.16 (95% CI: 4.46–8.50) and 2.86 (95% CI: 2.41–3.39) times higher in FH2 and FH1, respectively, than in FH0 after adjustment for classical risk factors for diabetes.ConclusionsFamily history risk categories of diabetes have a significant, independent, and graded association with the prevalence of this disease in the Chinese population.

Association between Serum Fibroblast Growth Factor-21 Levels and Nonalcoholic Fatty Liver in Korean Men with Type 2 Diabetes

목적: 혈청 FGF-21의 증가는 비만, 대사증후군, 제2형 당뇨병을 가진 환자에서 관찰되었으나 현재까지 제2형 당뇨병환자에서 NAFL과 FGF-21의 연관성은 확실하게 정립되어 있지 않다. 이에 저자들은 제2형 당뇨병을 가진 한국인 남성환자에서 혈중 FGF-21 수치와 NAFL의 연관성을 확인하고 혈중 FGF-21 수치에 영향을 미치는 독립적 위험인자를 알아보고자 하였다. 방법: 제2형 당뇨병으로 진단 받은 한국인 성인 남자 135명 (평균 56.2 ± 9.2세)을 대상으로 하였다. 임상 및 생화학적 대사 지표를 측정했고 혈청 FGF-21은 ELISA를 이용하여 측정했다. NAFL의 정도는 복부 초음파 검사를 통해 진단했으며 간 내 혈관 경계와 횡격막이 희미하게 보이거나 또는 보이지 않으면서 간 실질의 초음파 음영이 두드러지게 증가한 경우를 중등도 이상의 지방간으로 판정하였다. 결과: 정상간을 가진 환자에 비해 중등도 이상 지방간을 가진 환자에서 BMI, 허리둘레, HOMA-IR, TG, 간효소 및 혈청 FGF-21 수치가 유의하게 증가되어 있었다. 혈청 FGF-21은 BMI, 혈청 Cr, TG, 간효소 수치, 그리고, hsCRP와 양의 상관관계를 갖고, HDL 콜레스테롤과 음의 상관관계가 관찰되었다. 다변량 선형 회귀분석에서 TG, 중증도 이상의 지방간 그리고 혈청 Cr만이 FGF-21 농도와 통계학적으로 유의한 양의상관관계를 보였다. 로지스틱 회귀분석에서도 중등도 이상지방간 동반의 위험도는 혈청 Cr, TG, BMI 그리고 HOMA-IR을 보정하고 난 이후에도 혈청 FGF-21과 통계적으로 유의했다. 결론: 본 연구는 제2형 당뇨병을 가진 한국 남자 환자에서 NAFL과 혈중 FGF-21 농도가 독립적인 연관성이 있음을 확인했다.

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = -0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D.

Correlation between Homeostatic Model Assessment-estimated Insulin Resistance (HOMA-IR) with Asymmetric Dimethylarginine (ADMA) in Prehypertension

BACKGROUND: Not only hypertension, prehypertension has been reported to be linked with increased cardiovascular morbidity and mortality risks as well. Prehypertension has three-fold hypertension and two-fold cardiovascular risks. Pathomechanism that links hypertension with cardiovascular is related with endothelial dysfunction and insulin resistance. Endothelial dysfunction occurs when nitric oxide (NO) biological function was impaired, whereas shown by asymmetric dimethylarginine (ADMA). Subjects with prehypertension had higher insulin resistance events than normotension, whereas shown by homeostatic model assessment-estimated insulin resistance (HOMA-IR). This research was conducted to investigate the correlation of HOMA-IR with ADMA in prehyper- and normo-tension.METHODS: A cross-sectional comparative research was designed. Subjects were recruited and divided into prehyper- and normo-tensive groups. ADMA was measured using ELISA method, while HOMA-IR was calculated by the ratio of fasting insulin and glucose. Spearman 1-tail and Mann Whitney statistical analyses were performed.RESULTS: Comparing to normotensive group, elevated levels of HOMA-IR and ADMA in prehypertensive group were shown, but not significant. In prehypertensive group, we found significant correlation between HOMA-IR and ADMA.CONCLUSION: Insulin resistance and endothelial dysfunction was elevated in prehyper-compared to normotension.KEYWORDS: prehypertension, insulin resistance, endothelial dysfunction, HOMA-IR, ADMA

Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery

Ghrelin, an endogenous ligand of the GH secretagogue receptor that exerts orexigenic activity, is negatively correlated with body mass index (BMI) and insulin resistance. Conversely, low levels of adiponectin (ApN), a circulating adipocytokine with antidiabetic, antiatherogenic and anti-inflammatory properties, have been found in several insulin-resistant conditions. Although Cushing's syndrome causes several metabolic and hormonal changes leading to insulin resistance and central obesity, few data concerning the impact of glucocorticoid excess on ghrelin and ApN levels are so far available. We evaluated ghrelin and ApN levels in 14 women (age +/- SE 39.5 +/- 3.9 years, BMI +/- SE 25.8 +/- 1.4 kg/m2) with Cushing's disease (CD) at baseline and after successful transsphenoidal surgery (TSS) and in 14 age- and BMI-matched healthy women. Despite similar levels of fasting glucose, insulin, homeostatic model assessment-estimated insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) values, patients with CD had ghrelin levels lower than controls (117.8 +/- 21.5 vs. 269.6 +/- 51.4 pmol/l, P < 0.01), and ghrelin levels did not correlate with ACTH, cortisol, androgen and GH levels. Patients and controls showed similar ApN levels (11.1 +/- 1.6 vs. 11.5 +/- 2.0 mg/l), which correlated negatively with insulin, HOMA-IR and BMI and positively with QUICKI and high density lipoprotein (HDL)-cholesterol only in controls. At 10.2 +/- 0.7 months after successful TSS, patients showed a significant increase in ghrelin levels compared to pretreatment values (342.5 +/- 25.6 vs. 117.8 +/- 21.5 pmol/l, P < 0.005) along with significant modifications in BMI, insulin, HOMA-IR and HDL-cholesterol and no change in ApN levels. In two patients tested on days 2-4 after TSS, no modification in ghrelin and ApN levels was observed, despite a dramatic reduction in cortisol levels. Cortisol excess did not directly affect ghrelin and ApN levels in patients with CD. The observation that ghrelin levels were low during the active phase of CD and increased after recovery suggests that glucocorticoids may influence ghrelin levels indirectly by modulating adiposity and metabolic signals over the long term.