Indices Of Glucose Metabolism Research Articles

Associations between circulating bone-derived hormones osteocalcin, lipocalin 2, and glucose metabolism in patients with acromegaly

Objective The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism. Methods Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables. Results Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P 0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 (β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin (β=0.512, P<0.01). In the multivariate models, low LCN2 (β=-0.398, P=0.017) and elevated serum osteocalcin (β=0.553, P=0.001) were predictors for AUCINS, osteocalcin was a positive predictor of HOMA- β (β=0.519, P=0.004). GH (β=0.294, P=0.029) and IGF-1(β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly. Key words: Acromegaly; Osteocalcin; Lipocalin 2; Glucose metabolism

Study on insulin resistance, glycolipid metabolism, and sex hormones in patients with polycystic ovary syndrome

Objective To evaluate the insulin resistance of patients with polycystic ovary syndrome (PCOS) by hyperinsulin-euglycemic clamp test, and to explore the characteristics of glycolipid metabolism and sex hormone levels in PCOS patients with insulin resistance. Methods Seventy-three patients with PCOS and 27 healthy women with body mass index and age matched with PCOS patients who were admitted to the Department of Endocrinology of Affiliated Hospital of Zunyi Medical University from July 2017 to February 2019 were underwent hyperinsulin-euglycemic clamp test. All subjects were grouped according to glucose metabolic rate, body mass index, and homeostasis model assessment for insulin resistance (HOMA-IR), the changes and differences of glucose and lipid metabolism and sex hormone indexes in PCOS patients were analyzed. Results In the PCOS group, impaired glucose regulation accounted for 3.23% (1/31), and abnormal lipid metabolism for 9.68% (3/31). In the PCOS with insulin resistance group, impaired glucose regulation accounted for 7.14% (3/42). Abnormal blood lipid metabolism reached 47.62% (20/42), and 5 patients were diagnosed with metabolic syndrome, accounting for 11.90%. Correlation analysis showed glucose metabolic rate and body mass index, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, cortisol, triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), free androgen index (FAI), and glutamyl transpeptidase (GGT) were negatively correlated(all P<0.05), while positively correlated with high density lipoprotein-cholesterol (HDL-C; P=0.028). HOMA-IR was positively correlated with body mass index, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HbA1C, LDL-C (P<0.05), and negatively correlated with glucose metabolic rate and HDL-C (P<0.05). Body mass index and waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, triglyceride, and LDL-C (P<0.05) were positively correlated, and negatively correlated with glucose metabolic rate, HDL-C, and sex hormone binding globulin (SHBG; P<0.01). Multivariate linear stepwise regression analysis showed that body mass index, total cholesterol, triglyceride, and cortisol were principal factors affecting glucose metabolic rate. Fasting plasma glucose, fasting insulin, and systolic blood pressure were important factors influencing HOMA-IR. Glucose metabolic rate, HOMA-IR, HDL-C, while SHBG were still vital to body mass index. Conclusion FAI, SHBG, and cortisol may be involved in the insulin resistance development of PCOS patients, and PCOS patients with insulin resistance were more susceptible to metabolic disorders. Key words: Polycysic ovarian syndrome; Insulin resistance; Hyperinsulin-euglycemic clamp; Glycolipid metabolism; Sex hormone

Liver iron concentration is an independent risk factor for the prediabetic state in β-thalassemia patients

Beta-thalassemia major (β-TM) comprises a group of inherited blood disorders characterized by the reduced synthesis of β-globin chains. Iron overload following blood transfusion can affect major tissues involved in glucose metabolism, leading to different glucose metabolic disorders in these patients. The aim of the present study was to compare glucose metabolism and iron overload indices in β-TM patients with prediabetic and normoglycemic states. This analytical study was performed on 49 patients with β-TM (age > 18 years), receiving regular blood transfusions. The fasting plasma glucose (FPG) and glucose tolerance tests indicated 32 normoglycemic and 17 prediabetic cases. The serum levels of C-peptide, fructosamine, fasting serum insulin, and serum ferritin were measured. In addition, T2*-weighted magnetic resonance imaging (MRI) of the heart and liver was carried out. Glycemic metabolism indices, including quantitative insulin sensitivity check index (QUICKI) and homeostatic model assessment for insulin resistance (HOMA-IR), were also calculated. The HOMA-IR score was significantly higher, while the QUICKI score was significantly lower in prediabetic patients, compared to normoglycemic patients (median [IR], 2.59 [2.19] vs. 1.46 [1.03], p = 0.007; mean ± SD, 0.34 ± 0.03 vs. 0.37 ± 0.04, p = 0.01). On the other hand, β-cell function was not significantly different between the groups. The liver iron concentration (LIC) at a cutoff point of 5.82 mg/g dry weight showed 93% sensitivity and 70% specificity for differentiation of prediabetic and normoglycemic states (AUC, 0.81 [95% CI, 0.65–0.95]; p = 0.002). Based on the findings, HOMA-IR and QUICKI can be applied as useful glycemic metabolism indices for predicting prediabetic and normoglycemic states among β-TM patients. Also, LIC was an independent risk factor for the prediabetic state.

Associations of impaired glucose metabolism with chronic peridontitis in pre-diabetes patients

Objective To investigate the associations of impaired glucose metabolism and insulin resistance with chronic periodontitis in pre-diabetes patients. Methods A cross-sectional analysis was conducted and we included a total of 171 pre-diabetes patients aged 30-65 years, free of diabetes. pre-diabetes was defined as impaired fasting glucose (IFG) [fasting glucose (FG): 6.1-7.0 mmol/L] and/or impaired glucose tolerance (IGT) [oral glucose tolerance test (OGTT): 7.8-11.0 mmol/L]. Chronic periodontitis was defined according to Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) definition and the patients were divided into mild, moderate, and severe chronic periodontitis groups [mild: at least two interproximal sites with clinical attachment loss (CAL) ≥3 mm and at least two interproxima sites with probing depth (PD) ≥4 mm or 1 site with PD≥5 mm; moderate: at least two interproximal sites with CAL ≥4 mm and at least two interproxima sites with at least two interproximal sites with PD ≥5 mm; severe: at least two interproximal sites with CAL ≥6 mm and at least one interproxima site with at least two interproximal sites with PD≥5 mm]. A periodontal examination indexes [plaque index (PLI), PD, CAL, and bleeding on probing (BOP)] and glucose metabolism indexes [FG, OGTT, hemoglobinA1c (HbA1c), fasting insulin and homeostasis model assessments of insulin resistance (HOMA-IR)] were measured. The association of glucose metabolism and chronic periodontitis was investigated by multivariable logistic regression analysis. Results FG in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, HOMA-IR in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, OGTT in the severe chronic periodntitis group was significantly higher compared with mild chronic peridontitis group and moderate chronic periodontitis groups, and there was no significant difference between moderate and mild chronic periodontitis groups. For the insulin and HbA1c, there was no significant difference among mild, moderate and severe chronic periodontitis groups. After multivariable adjustment of age, gender, smoking status, hypertension and body mass index, IFG (OR=1.39, 95%CI: 1.01-1.98) and HOMA-IR (OR=1.36, 95%CI: 1.04-1.76) were associated with moderate periodontitis; IFG (OR=1.64, 95%CI: 1.17-2.40), IGT (OR=1.65, 95%CI: 1.21-2.26), and HOMA-IR (OR=1.72, 95%CI: 1.23-2.41) were significantly associated with severe periodontitis. Conclusion Our data provided evidences that impaired glucose metabolism were associated with chronic periodontitis among pre-diabetes patients.

Transendothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice.

The continuous endothelium of skeletal muscle (SkM) capillaries regulates insulin's access to skeletal myocytes. Whether impaired transendothelial insulin transport (EIT) contributes to SkM insulin resistance (IR), however, is unknown. Male and female C57/Bl6 mice were fed either chow or a high-fat diet for 16 weeks. Intravital microscopy was used to measure EIT in SkM capillaries, electron microscopy to assess endothelial ultrastructure, and glucose tracers to measure indices of glucose metabolism. Diet-induced obesity (DIO) male mice were found to have a ~15% reduction in EIT compared with lean mice. Impaired EIT was associated with a 45% reduction in endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with sustained interstitial insulin delivery, DIO male mice still showed SkM IR indicating severe myocellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure, or SkM insulin sensitivity between lean female mice and female mice fed a high-fat diet. These results suggest that, in male mice, obesity results in ultrastructural alterations to the capillary endothelium that delay EIT. Nonetheless, the myocyte appears to exceed the endothelium as a contributor to SkM IR in DIO male mice.

Effect of obstructive sleep apnea syndrome on glycolipid metabolism and early atherosclerosis in diabetics

ObjectiveTo study the changes in glucose and lipid metabolism indexes and the condition of early atherosclerosis in patients with diabetes with and without obstructive sleep apnea syndrome (OSAS). MethodsPatients with type 2 diabetes mellitus (DM) aged 32–50 years who did not have significant complications were included. A total of 42 patients with DM with OSAS and 46 patients with DM without OSAS were chosen according to their sleep monitoring indexes. Height and weight were measured, and fasting blood glucose, postprandial blood glucose, endothelin (ET), nitric oxide (NO) and lipid profile were tested. Then, all the subjects were subjected to the pulse wave velocity (PWV) test. ResultsThe levels of glycated haemoglobin and triglycerides were significantly higher in patients with DM with OSAS than those in patients with DM without OSAS. ET, NO and PWV changed significantly. ConclusionPatients with diabetes with OSAS are more likely to have complications related to arteriosclerosis and aggravation of glycolipid metabolism disorder. Early intervention is recommended.

Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome

AbstractThis study was performed to elucidate the potential influence of He Qi San (HQS) on glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients with phlegm-blood stasis syndrome (PBSS), and to determine DNA methylation changes. Sixty T2DM patients with PBSS were randomly divided into control and HQS groups. The control group received conventional treatments, and the HQS group received conventional treatments plus HQS. Glucose metabolism (FPG, 2hPG, FINS, and HbA1c) and lipid metabolism indexes (TG, TC and LDL-C) were determined. Genes with differential DNA methylation were subjected to GO and KEGG analyses. Glucose and lipid metabolism indexes in both groups were reduced, but were much more pronounced in the HQS group. Differential promoter CpG methylation regions were identified in 682 genes, including 426 genes with high-CpG promoters, 150 genes with intermediate CpG promoters, and 106 genes with low CpG promoters. Genes with differential DNA methylation were mainly enriched in the AMPK and insulin signaling pathways, terpenoid backbone biosynthesis, and renin secretion. We concluded that HQS remarkably improved indexes of glucose and lipid metabolism in T2DM patients with PBSS through regulating the DNA methylation of genes in the AMPK and insulin signaling pathways and terpenoid backbone biosynthesis.

Early development of decreased β‐cell insulin secretion in children and adolescents with hemoglobin H disease and its relationship with levels of anemia

Diabetes mellitus (DM) associated with iron overload has been reported among adults with transfusion-dependent thalassemia and those with non-transfusion-dependent thalassemia (NTDT), especially in β-thalassemia disease. However, little is known about glucose metabolism and how early its dysregulation can develop in α-thalassemia hemoglobin H (Hb H) disease, which is one of the most common types of NTDT worldwide. We prospectively calculated glucose metabolism index in 40 patients (aged 10-25 years) with Hb H disease. Glucose metabolism data were compared between patients with deletional versus nondeletional Hb H, and between patients with normal versus abnormal insulin secretion/sensitivity. Despite normal glucose tolerance in all patients, 52.5% had abnormal insulinogenic index indicating decreased β-cell insulin secretion. Patients with functional hemoglobin < 8 g/dL had significantly higher percentages of abnormal insulinogenic index. There was no significant difference in abnormal insulinogenic index between deletional and nondeletional Hb H. Decreased β-cell insulin secretion is highly prevalent among children and adolescents with Hb H disease, and it is associated with levels of functional anemia at baseline, but not with the type of Hb H disease. This result warrants heightened awareness among hematologists due to potentially increased risk of DM later in life.

Effects of acute hyperglycaemia stress on indices of glucose metabolism and glucose transporter genes expression in cobia ( Rachycentron canadum )

The objective of the present study is to preliminarily clarify the mechanism of carbohydrates metabolism in cobia (Rachycentron canadum) (85 ± 3 g) receiving injection of glucose solution. We examined plasma glucose (GLU), total protein (TP), triglyceride (TG), cholesterol (CHOL), insulin, liver glycogen and muscle glycogen, activities of hepatic hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK), as well as relative expressions of glucose transporter 1 (GLUT1), GLUT2, GLUT3, GLUT4, GLUT5 and GLUT9 in hemocyte, liver and muscle of R. canadum when fish were injected with 200 μl of glucose solution (255 mg/ml) after 0, 1, 2, 4, 8, 12, 24 and 48 hr. Fish received injection of 0.68% saline served as control. Results indicated that the plasma GLU, TG and CHOL increased and reached peak at 1, 8 and 48 hr postinjection (hpi) respectively. The hepatic glycogen increased from 1 hpi, and reached peak at 8 hpi, plasma insulin increased at 1 hpi, and reached peak at 2 hpi, and activity of hepatic PK peaked at 8 hpi. Furthermore, the relative expressions of GLUT1, GLUT2, GLUT3, GLUT4 and GLUT5 in hemocytes reached peak at 1,4, 8, 4 and 8 hpi, respectively, relative expressions of GLUT2, GLUT3, GLUT5 and GLUT9 in liver reached peak at 24, 24, 12 and 24 hpi, respectively, and relative expressions of GLUT1 and GLUT3 in muscle were significantly higher at 2 and 2–4 hpi, respectively compared with those in controls. In conclusion, low ability of utilizing glucose in R. canadum may be attributed to insufficient insulin secretion, low activities of key glycolytic enzymes (HK, PFK and PK) regulated by glucose injection and slow increase of GLUTs.

Sex differences in the prevalence and adverse outcomes of sarcopenia and sarcopenic obesity in community dwelling elderly in East China using the AWGS criteria

BackgroundSarcopenia and sarcopenic obesity (SO) have a greater impact on the elderly. This study aimed to explore whether there were sex differences in the prevalence and adverse outcomes of sarcopenia and SO in community-dwelling elderly individuals in East China.MethodsThis was a cross-sectional study that enrolled 213 males and 418 females aged > 65 years. Demographic characteristics, body composition, hand grip, gait speed, and indices of glucose and lipid metabolism were collected. Sarcopenia and SO were diagnosed using the Asian Working Group for Sarcopenia criteria.Results(1) The prevalence of sarcopenia was 19.2% in males and 8.6% in females. The prevalence of SO was 7.0% in males and 2.4% in females. (2) In males, the odds ratios (ORs) of osteoporosis and dyslipidemia in the SO group were 4.21-fold and 4.15-fold higher than those in the normal group, respectively. In females, the ORs of osteoporosis and hyperglycemia in the SO group were 1.12-fold and 4.21-fold higher than those in the normal group.ConclusionsMales were more likely to be sarcopenic and to have SO than females using the AWGS criteria. Females with SO were more likely to have higher blood glucose, whereas males with SO were more likely to have osteoporosis and dyslipidemia.

Myeloid-derived growth factor improves blood glucose level in type 2 diabetic mice by promoting glucagon-like peptide 1 secretion

Objective To investigate the effect of myeloid-derived growth factor(MYDGF)on the secretion of glucagon-like peptide 1(GLP-1)in type 2 diabetic mice and its mechanism. Methods A type 2 diabetes model was established by injecting streptozotocin into C57BL/6J wild type(WT)mice and MYDGF knockout(KO)mice, which were divided into diabetic group(WT-D, KO-D)and non-diabetic group( WT-ND, KO-ND). Six weeks later, the relevant indicators were detected. Next, those mice were divided into wild-type diabetes group(WT-GFP), wild-type diabetes MYDGF intervention group(WT-MYDGF), knockout type diabetes group(KO-GFP), and knockout type MYDGF intervention group(KO-MYDG)according to whether or not the AAV-MYDGF intervention was performed. The wild-type non-diabetic mice were used as a blank control group to observe the effects of MYDGF on biochemical indexes, GLP-1 secretion, and mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK)signal pathway in mice. Results After 6 weeks of intervention, there was no significant difference in the glucose and lipid metabolism indexes between WT-ND and KO-ND groups(P>0.05). Compared with WT-D group, fasting plasma glucose(FPG), HbA1C, and blood lipid levels in KO-D group were increased, while gcg, pc3 mRNA, and GLP-1 secretion levels were decreased(all P<0.05). Compared with the WT-GFP group, FPG, HbA1C, and blood lipid levels were decreased in WT-MYDGF group, while gcg and pc3 mRNA, and GLP-1 secretion levels were increased(all P<0.05). KO group revealed a result similar to that in WT group after MYDGF intervention. Western blotting showed that the phosphorylation level of ERK1/2 was lowered in KO diabetic mice compared with WT diabetic mice, which was enhanced in WT and KO mice after MYDGF intervention. Conclusions MYDGF promotes the secretion of GLP-1 by activating MEK/ERK signaling pathway, thereby delaying the development of diabetes. Key words: Myeloid-derived growth factor; Diabetes mellitus, type 2; Glucagon-like peptide-1

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study

PurposeThe aim of this study was to evaluate the blood pressure–lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. MethodsThis study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non–HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. FindingsThe percentage changes of LDL-C were −48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and −49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non–HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, −8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. ImplicationsOnce-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261.

Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes

We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n = 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status (normoglycemic [n = 534]/impaired fasting glucose [IFG] [n = 252]/type 2 diabetes [T2D] [n = 24]) determined. Levels of hsa-miR-144-5p, -122-5p, -148a-3p, -589-5p, and hsa-let-7a-5p associated with glycemic status. hsa-miR-144-5p and -148a-3p associated with glucose levels, while hsa-miR-144-5p, -122-5p, -184, and -339-3p associated with insulin levels and HOMA2-IR, and hsa-miR-148a-3p, -15b-3p, -93-3p, -146b-5p, -221-3p, -18a-3p, -642a-5p, and -181-2-3p associated with HbA1c levels. The targets of hsa-miR-146b-5p that correlated with its levels were enriched in inflammatory pathways, and the targets of hsa-miR-221-3p were enriched in insulin signaling and T2D pathways. These pathways showed indications of co-regulation by HbA1c-associated miRNAs. There were significant differences in the microRNA profiles associated with glucose, insulin, or HOMA-IR compared to those associated with HbA1c. The HbA1c-associated miRNAs also correlated with the expression of target mRNAs in pathways important to the development of T2D.

2471-PUB: Evaluation of Model-Based Indices of Glucose Metabolism in Morbidly Obese Subjects

Patients with MO are insulin resistant and the degree of insulin resistance (IR) further depends on glycemic status. To determine IR, model-based indices use fasting and/or post-challenge glucose and insulin levels. In this study, we examined the validity of indices of GM in a large cohort of patients with MO and varying degrees of glucose tolerance. We included 1337 patients with MO without known diabetes (mean age 40±12 years, mean±SD, BMI 45.0± 6.6kg/m²). All patients underwent a 75g oGTT, glucose and insulin levels were repeatedly measured for the calculation of IR and Insulin Sensitivity indices (Table) and analysis for the respective glucose tolerance categories. Diabetes mellitus (DM) was detected in 120 (9%) patients, 348 (26%) had impaired glucose tolerance or impaired fasting glucose (IGT/IFG), 869 (65%) patients had normal glucose tolerance (NGT). Patients with DM were older (p&amp;lt;0.001) and had a lower BMI (p= 0.014) compared to NGT. GM indices are depicted in the Table. and show that all indices except for Matsuda and AUC insulin show differences between the glucose tolerance categories. In patients with MO, GM indices using basal glucose and insulin levels can be used to routinely measure insulin resistance without need of more elaborate testing. In particular, they can be used in patients with diabetes when an OGTT would be inappropriate. Disclosure J. Brix: None. E. Krzizek: None. A. Tura: None. G. Pacini: None. B. Ludvik: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Sanofi, Takeda Development Centre Europe Ltd. Research Support; Self; Akebia Therapeutics, Eli Lilly and Company, Novartis AG, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp.

Glucometabolic characteristics and higher vascular complication risk in Korean patients with type 2 diabetes with non-albumin proteinuria

ObjectiveWe investigated the clinical relevance of non-albumin proteinuria (NAP) in Korean patients with type 2 diabetes (T2D). Research design and methodsWe enrolled 883 T2D patients who had both their urinary albumin-to-creatinine ratio (uACR) and protein-to-creatinine ratio (uPCR) measured. We classified the patients into non-proteinuria (NP; uPCR <150 mg/g and uACR <30 mg/g), isolated NAP (iNAP; uPCR ≥150 mg/g and uACR <30 mg/g), and albuminuria (uACR ≥30 mg/g) groups. The associations between uPCR, uACR, and several indices of glucose metabolism were investigated. ResultsThe glucometabolic pathophysiology of iNAP (96 [10.9%]) group was more associated with a decrease in homeostatic model assessment (HOMA)-beta value (aOR 1.89 [95% CI, 1.21–2,96]) than with an increase in HOMA-insulin resistance (aOR 1.29 [95% CI, 0.83–2.01]). uPCR ≥150 mg/g was also found to have more consistent and stronger association with vascular complications than uACR ≥30 mg/g (aOR 1.44 [95% CI, 1.03–2.02] vs. 1.26 [95% CI, 0.89–1.79]). ConclusionsThe nephropathy of iNAP may be mainly attributed to decreased beta cell function. Furthermore, uPCR might be a more sensitive urinary biomarker than uACR for the detection of vascular complications in T2D patients.

Effects of resistant starch of mixed tubers snacks on glucose metabolism, leptin, visceral fat and body mass index in type 2 diabetes mellitus (T2DM)

Resistant starch could lower blood glucose, decrease adipocyte in adipose tissue and affect satiety hormones such as leptin. Tubers and pumpkin have high content of resistant starch, but their effectiveness to type 2 diabetes mellitus (T2DM) has not been known clearly. This research was conducted to determine the effectiveness of snack consumption made from tubers and pumpkins to BMI, visceral fat, glucose and leptin levels in the blood of T2DM patients and the correlation between the variables. The research method was pre-post clinical trial. Sixteen T2DM patients were in treatment (RS) and control groups. Subjects in RS group were given snack twice daily for 4 weeks. After following wash out process for 4 weeks, the same subjects was continued as subjects’ control. Paired t-test and/or Wilcoxon-test was used to analyze the differences between values before and after treatment in the group and between groups. Pearson test was used to analyze the correlation of BMI, visceral fat, glucose and leptin level. The visceral fat was increased in RS group (p=0.04) after 4 weeks consuming snack but decrease in control group (p=0.04) without significant change of BMI. Leptin level was decreased (p=0.00) in RS group. Blood glucose significantly decreased (p=0.01) and leptin level increased slightly in control group. Comparing the RS and control group at the end of study, there were significantly different in the variation of visceral fat in the female groups (p=0.05) and leptin (p=0.05). Visceral fat correlated with BMI in the RS and control group. In conclusion, the mixed tubers and pumpkin snack decreased the leptin level but increased visceral fat.

Dealing with complexity in type 2 diabetes

The management of people with type 2 diabetes (or type 2 diabetes mellitus) can be complex and sits largely within the portfolio of primary care. Unfortunately, despite an ever-increasing therapeutic armoury, many people with type 2 diabetes fail to achieve optimal control of their blood glucose and other metabolic indices, putting them at higher risk of diabetes-related complications. The situation has sadly changed little over recent years. People with type 2 diabetes often have other long-term health concerns that need to be recognised and addressed alongside more traditional parameters such as blood glucose and blood pressure. In this article, we will consider the recognition and management of two of the more common conditions that co-exist in people with type 2 diabetes: Diabetes distress and renal disease. Although there is undoubtedly some overlap with type 1 diabetes, the discussion in this article solely relates to the management of type 2 diabetes.

Influence of Maternal Factors (Weight, Body Condition, Parity, and Pregnancy Rank) on Plasma Metabolites of Dairy Ewes and Their Lambs.

Simple SummaryThe present study assessed the effects of maternal parity, weight, body condition score (BCS), and pregnancy rank (single vs. multiple) on maternal metabolism during pregnancy and subsequent lactation, as well as on lamb birth weight, perinatal viability, and metabolism. The results highlight the relevance of appropriate nutritional management to maintain maternal BCS and offspring metabolism within physiological ranges, allowing sheep to face the metabolic challenges of lactation and pregnancy. Adequate nutrition and management reduce the influence of maternal factors on offspring phenotype.Pregnancy and lactation are challenging states that affect maternal and lamb health. In Lacaune dairy sheep, we evaluated the impact of parity, pregnancy rank, and body condition on body weight and the condition of ewes and lambs in mid-pregnancy (75 ± 5 d), in late pregnancy (142 ± 4d), and postpartum (52 ± 5d pp). Maternal age was associated with initial decreases, followed by increases, in body weight and condition. After lambing, both mature and maiden ewes lost weight and body condition. Maternal indices of glucose, protein, and lipid metabolism were within physiological values during pregnancy, but postpartum values depended on maternal parity and pregnancy rank, with multiple-pregnant ewes showing a postpartum increase in glucose and maiden sheep a postpartum increase in plasma cholesterol concentration. Male lambs were heavier than female lambs at birth, and lambs born to mothers with higher body condition scores were heavier. Lambs born as singletons were heavier than those born in litters. Maternal age and pregnancy rank did not influence lamb metabolic indicators. Sex affected plasma concentrations of glucose, triglycerides, and cholesterol. Maternal metabolic indicators showed minimal effects on lamb phenotype. These results suggest that, when appropriately fed, dairy sheep can cover the metabolic demands of pregnancy and milk production, regardless of age and pregnancy rank.

Adipokines and macrophage markers during pregnancy-Possible role for sCD163 in prediction and progression of gestational diabetes mellitus.

The risk of gestational diabetes mellitus (GDM) is increased in overweight and obese women potentially involving secreted mediators from adipose tissue. Our main aim was to evaluate if circulating adipokines and monocyte/macrophage markers were dysregulated in GDM and the influence body mass and indices of glucose metabolism had on this association. We further explored if early detection of these markers improved prediction of GDM and if they remained modified during long-term follow-up. Population-based prospective cohort study in 273 pregnant women with markers measured four times during pregnancy and at 5-year follow-up. sCD163 was higher (25% at 14-16weeks, P<0.001) and adiponectin lower (-17% at 14-16weeks, P<0.01) early in pregnancy and at 5-year follow-up in GDM women, independent of BMI, and other GDM risk factors. Leptin, adiponectin, and chemerin were robustly associated with glucose metabolism throughout pregnancy while sCD163 was inversely associated with β-cell function early in pregnancy in women with increased BMI. Finally, the markers at 14 to 16weeks displayed modest discriminatory properties with regard to prediction of GDM (AUC<0.7). Using a combination of fasting glucose and sCD163, 53% of GDM could be identified when 25% of the population scored positive suggesting some merit in a multimarker approach. sCD163 and adiponectin were dysregulated in GDM, independent of body mass. None of the adipokines or monocyte/macrophage activation markers displayed clinically useful properties alone for early detection of GDM. Activation of monocytes/macrophages may be an important event in the early development of GDM.

Decreased beta-cell function in breastfeeding obese and non-obese women: A prospective observational study

Obesity is associated with lower breastfeeding rates. The underlying pathophysiological mechanisms are not well-understood, but there is increasing evidence on an association between parameters of maternal glucose metabolism and prolactin concentrations. In this cross-sectional observational study we investigate the relationship between breastfeeding, maternal obesity, and maternal glucose metabolism postpartum with beta cell function as a primary outcome measure. We investigated 106 women (44% obese) prospectively recruited during the pregnancy, who underwent a 75g - 2h oral glucose tolerance test (OGTT) between the 3rd and 5th months postpartum. At this time point, we tested the relationship between breastfeeding status, maternal prolactin concentrations, maternal obesity, and fasting and dynamic indices of glucose metabolism using multivariate logistic regression in a post hoc analysis of prospective observational data. During the study visit at a mean of 122 (SE 9.3) days after delivery, 47% of obese women and 68%of non-obese women were breastfeeding (p<0.05). Lactation and higher prolactin concentrations were associated with lower prepregnancy weight and lower postpartum insulin concentrations. Prehepatic beta-cell function was decreased in both obese (mean (SD); 0.16 (0.04) vs. 0.19 (0.05), p<0.05) and non-obese (0.12 (0.05) vs. 0.16 (0.06), p<0.01), lactating women. Obese lactating women have significantly lower first (1135.1 (306.7) pmol/L vs. 1517.3 (475.8) pmol/L, p<0.01) and second phase insulin secretion (mean (SD), 300.2 (70.7) pmol/L vs. 393.1 (115.5) pmol/L, p<0.01) as shown by Stumvoll indices when comparing to obese non-lactating women. Prehepatic beta-cell function and Stumvoll 1st phase insulin secretion index, but not BMI, were independently and negatively associated with breastfeeding and circulating prolactin concentrations. Beta-cell function during lactation relates to breastfeeding and circulating prolactin concentrations independently of obesity. The well-known positive effects of lactation on maternal and offspring outcomes might reflect a causative relationship of higher breastfeeding rates in metabolically healthier women.