Decreased Insulin Resistance Research Articles

Sclerostin and its association with insulin resistance in children and adolescents.

Recent studies have shown that sclerostin, which is mainly known as a negative regulator of bone formation, could play an important role in the crosstalk between bone and glucose metabolism. The aim of this study was to investigate the relationship between sclerostin, other bone and fat related factors as osteocalcin (OC), Receptor Activator of Nuclear Factor NF-қB ligand (RANKL), leptin and adiponectin with glucose metabolism and insulin action in children and adolescents with obesity compared with healthy children and adolescents. Fifty-five obese children and adolescents, a mean age of 13.2 ± 3.4 yrs., BMI 28.89 ± 5.5 kg/m2, and 26 healthy controls (mean age 13.0 ± 4.3 yrs., BMI 19.96 ± 3.1 kg/m2), sex-, and Tanner stage-matched were included into the study. Fasting blood samples for measurement of sclerostin, glucose, lipid profile, HbA1c, C-peptide, OC, RANKL, leptin and adiponectin, and vitamin D were taken at 8.00 AM. Sclerostin, osteocalcin, RANKL, and adiponectin levels did not differ between obese patients and the control group. Leptin and fasting insulin levels were significantly higher in obese subjects compared with controls (p < 0.01, p = 0.01, respectively). A positive correlation between sclerostin and OC (r = 0.417, p = 0.027) and negative correlations between sclerostin and HOMA-IR and between sclerostin and age (r = -0.24, p = 0.045, r = -0.23, p = 0.037, respectively) were found in all of the subjects. Sclerostin did not correlate with HbA1c, lipids, RANKL and fat-derived leptin and adiponectin. Partial correlation analysis adjusted for age, SDS-BMI and Tanner staging only revealed a negative correlation between sclerostin and HOMA-IR (r = -0.3, p = 0.01). In obese patients this correlation was stronger than in the whole group (r = -0.39, p = 0.005). Moreover, a negative correlation between sclerostin and insulin was found in obese patients (r = -0.39, p = 0.006). In the healthy cohort, sclerostin had a negative correlation only with C-peptide (r = -0.79, p = 0.02). Sclerostin could play an important role in the regulation of glucose metabolism in children and adolescents, regardless of other fat and bone-derived factors. In obese young patients it's action could be associated with decreasing insulin resistance.

Insulinomimetic Effect of Citrullus Colocynthis Roots in STZ Challenged Rat Model

Abstract Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from either defect in insulin secretion, insulin action, or both. Postprandial hyperglycemia is a prime characteristic of diabetes mellitus and has been a focus in the therapy for diabetes. One of the therapeutic approaches which involve decreasing hyperglycemia aims at lowering blood glucose by decreasing insulin resistance, raising insulin sensitivity at the tissues and inhibiting the carbohydrate absorbance in the intestine. Plants contain different chemical constituents with potential for insulin mimetic action, decrease in insulin resistance and of α-amylase inhibitory activity may be used as therapeutic agents in the treatment of diabetes mellitus. The present study investigates the hypoglycemic activity and insulinomimetic action of aqueous and ethanolic extracts of Citrullus colocynthis by invitro α-amylase enzyme inhibition and by histopathological studies in streptozotocin (STZ) induced diabetic rats. Male Wistar rats weighing about 180- 250g were taken and divided into fifteen groups. Diabetes was induced by giving streptozotocin (STZ) (30-50mg/kg) intraperitoneally. Rats that showed blood glucose levels > 250mg/dl were selected for the study. Metformin (45mg/kg) was given as standard oral hypoglycemic agent. The aqueous and ethanolic extracts of Citrullus colocynthis (AECC and EECC) at 100mg/kg, 200mg/kg and 300mg/kg were administered to the normal and diabetic rats. The invitro α – amylase inhibitory activity was done by spectrophotometric method. Blood glucose levels were measured by glucose oxidase method. Estimation of glycogen in the lever was carried out with anthrone method. Liver and pancreas were isolated and subjected to histopathological studies. Serum insulin was monitored through chemiluminescence assay. Oral administration of both extracts showed significant inhibition of α-amylase enzyme in-vitro and decrease in blood glucose also. Glycogen and Insulin levels too were found to increase in extract treated groups which attributed for its insulinomimetic activity. The findings revealed that Citrullus colocynthis possess a very strong anti-hyperglycemic potential justifying the use of the drug for the treatment of diabetes mellitus.

Effects of silymarin on metabolic syndrome: a review.

Metabolic syndrome is one of the rising global health problems and medical challenges due to several clinical complications it may cause, for example increasing the risk of myocardial infarction and hypertension. However, great attention has been directed toward determining the worthiness of herbal medicines. There are emerging studies on preventive and therapeutic effects of silymarin on different components of metabolic syndrome. Extracted from the dried seeds of milk thistle plant (Silybum marianum L.), silymarin has been used in the treatment of different diseases for many years. Several protective effects have been identified for this herb such as decreasing insulin resistance, regulating blood pressure and lipid profile, as well as antioxidant and cytoprotective effects. This review aims to discuss available human and experimental researches into the promising effects of silymarin on different elements of metabolic syndrome. All related human and experimental papers published from 2012 to date were included in this review. Reviewing different human and experimental studies into the effects of silymarin on metabolic syndrome, we deduced that silymarin possesses promising effects on different components of this syndrome. Although the complete mechanism of action and target organs for silymarin require further verification and investigation, high-risk individuals may benefit from supplementation with this herbal medicine. © 2018 Society of Chemical Industry.

IMG-1 Lowers Insulin Resistance by Decreasing Hepatic Glucose Production in a DIO Mouse Clamp Test

IMG-1 is a novel therapeutic compound for the treatment of diabetes. IMG-1 has been shown to successfully treat both type 1 mice and rats (STZ models) and type 2 ZDF rats. To test how IMG-1 is able to treat type II diabetes, diet-Induced Obese (DIO) C57BL/6J mice were used in a hyperinsulinemic-euglycemic clamp assay. The hyperinsulinemic-euglycemic clamp is the gold-standard method to assess insulin sensitivity. The euglycemic clamp is widely used in clinics and laboratories to measure insulin action on glucose utilization in humans and animals for clinical and basic science research. Sixteen DIO C57BL/6J mice underwent a 2-hour hyperinsulinemic-euglycemic clamping to assess insulin action and glucose metabolism in IMG-1 treated (2µg IMG-1 administered IV via tail vein 48 and 24hours prior to the clamp test, n=8) or PBS treated animals (n=8). IMG-1 treated animals had significantly higher steady-state glucose infusion rates during clamping than PBS treated animals, indicating that IMG-1 is able to decrease insulin resistance in DIO mice. IMG-1 did not affect whole-body glucose turnover, glycolysis or glycogen synthesis in any of the treated animals. Glucose metabolism in skeletal muscle and adipose tissue was not significantly different in either IMG-1 or PBS treated animals during the clamp assay. However, Hepatic Glucose Production (HGP) was dramatically suppressed in all animals treated with IMG-1 (a decrease from 3.mg/kg/m to -6.16 mg/kg/m). Furthermore, hepatic insulin action (the percent suppression of HGP) was increased in all IMG-1 treated animals&amp;#x2028;during the hyperinsulinemic-euglycemic clamp (from 70.9 control to 99.7 IMG-1). IMG-1 is a novel compound for the treatment of diabetes. These results show that IMG-1 decreases insulin resistance in a type 2 diabetic mouse model by suppressing HGP and increasing hepatic insulin action. Disclosure J.B. Pollett: Employee; Self; Imagine Pharma. H. Noh: None. J.K. Kim: None. N. Thai: Board Member; Self; Imagine Pharma.

IMG-1 Reduces Blood Glucose Levels in Type 1 Diabetic Animal Models

IMG-1 is a novel compound that has been shown to successfully treat type 2 diabetes in ZDF rats and decrease insulin resistance by suppressing HGP and increasing hepatic insulin action in DIO mice. To test the efficacy of IMG-1 to treat type I diabetes Streptozotocin (STZ)-induced diabetic models were employed. In the first study C57BL/6J mice were treated with STZ (50mg/kg) for 5 days to induce diabetes. The animals were either administered IMG-1 or PBS via oral gavage daily for 29 days. Blood glucose (BG) levels were evaluated three times weekly and insulin was measured twice weekly. After 17 days of treatment, IMG-1 treated animals displayed a significant decrease in BG levels (200-300 mg/dl) that persisted for the remainder of the study, while the control animals had continuously high BG levels (400-600 mg/dl). Insulin levels were low in these animals and unaffected by IMG-1. This finding was mimicked in a second experiment where a STZ rat model was used where Sprague-Dawley rats were given a single injection of STZ (60mg/kg) to induce diabetes. In the rat model, the IMG-1 treated animals had significantly lower BG levels by day 9 and remained low for the entire study (200-300 mg/dl). Total bilirubin, ALP, ALT, AST, BUN and creatinine levels were assessed following the 29-day study to determine liver and kidney toxicity. Bilirubin, BUN and creatinine levels were within the normal range, while the ALP, ALT and AST levels were elevated with the STZ treatment (common in this model). IMG-1 did not have any effect on the liver enzymes compared to control. IMG-1 can regulate BG levels in type I diabetic animal models and does not affect kidney or liver function. Disclosure J.B. Pollett: Employee; Self; Imagine Pharma. H. Noh: None. J.K. Kim: None. N. Thai: Board Member; Self; Imagine Pharma.

High Maternal DHA Levels in Hawaiian Women Decrease Insulin Resistance

Obesity prevalence during pregnancy (PG), a significant risk factor for metabolic inflammation and subsequent increase in insulin resistance (IR), has increased ∼ 35% in the last 20 years. Offspring of obese (OB) women are at a higher risk of metabolic dysfunction. Omega-3 fatty acids such as DHA have been shown to decrease IR in animals, though the effects of DHA in PG women are unclear. We hypothesize that high plasma DHA levels are associated with lower IR in PG women in an environment of high omega-3 intake (Hawaii), but differ in metabolic effect in OB vs. lean (LN) women. We evaluated 54 healthy, normal glucose tolerant women and their offspring at term elective C-section in Honolulu. We grouped subjects according to their pre-PG BMI into LN and OB. We measured maternal plasma insulin, glucose, C-reactive protein (CRP), and DHA concentration (gas chromatography/mass spectrophotometry) and calculated the homeostatic model assessment for IR (HOMA-IR). As expected, IR was higher in OB women (Table 1). Maternal DHA was negatively correlated with maternal HOMA-IR (R2= 0.25 p = 0.001), and CRP (R2=0.15 p= 0.004) among all women. These correlations persisted for OB women: HOMA-IR (R2=38 p=0.0007), CRP (R2=0.20 p=0.01); but not for LN women. High maternal DHA is associated with lower inflammation and IR in OB PG women at term. We speculate that high pre-PG omega-3 intake has a significant metabolic impact on insulin sensitivity, especially in OB women.Table 1Lean (BMI: 16-24.9 kg/m2 n=29)Obese (BMI&amp;gt;30, n=26)P.valueGestational Age at delivery (wks)38.8 ± 0.639.1 ± 0.40.088Pre-Pregnancy BMI (kg/m2)21.1 ± 2.236.8 ± 6.9&amp;lt;0.0001DHA (µmol/L)453 ± 187347 ± 1200.02HOMA IR1.1 ± 0.82.4 ± 1.4&amp;lt;0.0001CRP (ng/mL)5180 ± 2688 7859 ± 23180.0005Birth Weight (kg)3.3 ± 0.43.5 ± 0.40.04 Disclosure F. Alvarado: None. P. Tsai: None. J. Minium: None. P. Catalano: None. P. O'Tierney-Ginn: None.

IMG-1 Is Able to Normalize Blood Glucose Levels by Inhibiting Glucagon Levels in a Type 2 Diabetic Rat Model

IMG-1 is a novel therapeutic compound for the treatment of diabetes. Ten-week-old diabetic ZDF rats were treated with IMG-1 either intravenously (IV) or per oral (PO) once a day and compared to no treatment over a thirty-five-day period. Weights and glucose levels were monitored twice a week. IMG-1 treated animals showed a marked decrease in BG levels within a week, (average BG levels of 179mg/dl for IMG-1 (IV) and 135mg/dl for PO). This finding was enduring for the entire 35-day period. Untreated controls had significantly elevated BG levels throughout the study, with average levels exceeding 400 mg/dl (481 mg/dl). Hemoglobin A1c (Hb1Ac) was measured at days 0 and 35. IMG-1 treated animals had significantly lower Hb1Ac (IV, 9.7%-&amp;gt; 7.4%) and PO (10.8% -&amp;gt;7.5%) while the untreated group maintained increased Hb1Ac levels (10.2%-&amp;gt;12.3%). There was no significant difference in insulin levels between untreated and IMG-1 treated groups at any time point suggesting IMG-1 decreased insulin resistance. Glucagon levels were reduced in both IV and PO IMG-1 treated animals at days 15 (from 115pg/ml and 119pg/ml to 90pg/ml and 92pg/ml, respectively) and 35 (89pg/ml and 92pg/ml). Control animals had no significant difference in glucagon levels throughout the entire study. Based on these results, it appears that IMG-1 is able to normalize both blood sugar in ZDF animals and lower HbA1c and decrease glucagon levels without elevating insulin levels in these animals. Disclosure J.B. Pollett: Employee; Self; Imagine Pharma. N. Thai: Board Member; Self; Imagine Pharma.

Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated?

To provide a comprehensive review summarizing the existing evidence on the association between nonalcoholic fatty liver disease (NAFLD) and hypertension (HT) independent of other components of metabolic syndrome. We searched the literature through Medline and the Cochrane Library for studies evaluating the relationship between hypertension and fatty liver disease. Studies testing this association are limited, but agree that HT and fatty liver disease are inter-related independent of other components of the metabolic syndrome such as obesity and diabetes mellitus. Clinical evidence shows that NAFLD is associated with new-onset HT, whereas increased blood pressure is related to the development of fatty liver disease and the possible subsequent progression to liver fibrosis. Insulin resistance and activation of the renin-angiotensin-aldosterone system (RAAS) might provide potential pathophysiologic links between these clinical entities. Until further evidence is available, patients with HT should be meticulously evaluated and treated for fatty liver disease and vice versa. RAAS inhibitors have been tested in NAFLD, presenting a favorable profile by decreasing insulin resistance and fibrosis progression. NAFLD and HT are associated independent of traditional cardiovascular risk factors. Insulin resistance appears to be the main linking mechanism. Although RAAS inhibitors are the most beneficial treatment option for HT in patients with NAFLD, randomized studies on the administration of these agents in HT patients with NAFDL are warranted to provide optimal treatment options in these high cardiovascular risk individuals.

A new indanedione derivative alleviates symptoms of diabetes by modulating RAGE-NF-kappaB pathway in db/db mice

Accumulating evidence indicates that a number of tissues are damaged due to build-up of abnormal amount of Advanced Glycation End products (AGEs) in several diseases including diabetes. Currently AGE inhibitors are scarce in clinical use indicating a need for development of new anti-AGE agents. The aim of the current study is to identify the new AGE inhibitors and to decipher their mechanism of action for alleviating symptoms of diabetes in mice. Among several derivatives, one of the derivatives of indanedione, IDD-24 demonstrated highest inhibition of AGE formation and AGE mediated reactive oxygen species production in HepG-2 and mature 3T3-L1 adipocytes. In mice treated with IDD-24, reduction in serum AGE formation and expression of Receptor for AGEs (RAGE) was seen in IDD-24 treated db/db mice. In vivo, glycogen synthesis was also increased in muscle tissue. In adipocytes, anti-AGE agent restored AGEs' induced diminished glucose uptake in fat cells. Mice treated with IDD-24 exhibited increased glucose tolerance, increaed serum adiponectin levels and decreased insulin resistance. Deciphering mechanism of IDD-24 in diabetic mice, it was observed that nuclear factor-κB (NF-κB) and serine phosphorylation of Insulin receptor substrate-1 (IRS-1) declined, while diminished activation of c-Jun NH2-terminal kinase (JNK) appears to be partly responsible for restoration of insulin signaling. We conclude that IDD-24 can be a possible treatment target to address symptoms of diabetes.

Telephone-based nutrition coaching decreases insulin resistance in patients undergoing breast cancer treatment.

e22062Background: Higher levels of insulin in breast cancer patients at diagnosis correlate with worse prognosis, independent of body mass index (Goodwin, Ennis et al. 2002). Breast cancer patients...

Effects of exercise training on adipose tissue apelin expression in streptozotocin-nicotinamide induced diabetic rats

Apelin is an adipocyte-derived peptide that plays an important role in regulation of energy homoeostasis and decrease of insulin resistance. We investigated the effects of exercise training on adipose tissue apelin expression in streptozotocin-nicotinamide induced diabetic rats. In this experimental study, 38 male Wistar rats were assigned to 4 groups: sedentary non-diabetic, trained non-diabetic, sedentary diabetic and trained diabetic. Type 2 diabetes mellitus (T2DM) was induced by intraperitoneal injection of streptozotocin and nicotinamide in adult rats. The trained groups ran 8-week on treadmill progressively for 45 min at a speed of 24 m/min and a 5% grade. After the training period, an intraperitoneal glucose tolerance test was performed in addition to the measurement of blood lipids and plasma apelin levels. Apelin mRNA levels in visceral adipose tissue were also analyzed. Two-way repeated measures analysis of variance (ANOVA) and Pearson correlation coefficient was used for analyzing data. P < 0.05 was considered to be statistically significant. Results indicated a significant decrease of insulin resistance followed by a significant increase of plasma levels and mRNA expression of apelin in trained diabetic compared with sedentary diabetic rats. Furthermore, apelin levels did not correlate significantly with body weight and epididymal fat weight in trained diabetic rats. In conclusion, the findings revealed that chronic exercise training, independently of body weight and fat pad weight by decrease of insulin resistance can increase apelin levels in visceral adipose tissue, thereby attenuating the progression of diabetes and decreasing insulin resistance in T2DM rats.

Physical Activity and Diabetes.

Physical Activity and Diabetes.

The Benefits of Enhanced Recovery After Surgery Programs and Their Application in Cardiothoracic Surgery.

The perioperative care of the surgical patient is undergoing a paradigm shift. Enhanced Recovery After Surgery (ERAS) programs are becoming the standard of care and best practice in many surgical specialties throughout the world. ERAS is a multimodal, multidisciplinary, evidence-based approach to care of the surgical patient that aims to optimize perioperative management and outcomes. Implementation, however, has been slow because it challenges traditional surgical doctrine. The key elements of ERAS Pathways strive to reduce the response to surgical stress, decrease insulin resistance, and maintain anabolic homeostasis to help the patient return to baseline function more quickly. Data suggest that these pathways have produced not only improvements in clinical outcome and quality of care but also significant cost savings. Large trials reveal an increase in 5-year survival and a decrease in immediate complication rates when strict compliance is maintained with all pathway components. Years of success using ERAS in colorectal surgery have helped to establish a body of evidence through a number of randomized controlled trials that encourage application of these pathways in other surgical specialties.

Ellagic Acid Ameliorates Insulin Sensitivity and Hepatic Oxidative Stress in Diabetic Female Rats: A Potential Anti‐Oxidant Agent for Type II Diabetic Complications.

Hyperglycemia and insulin resistance are found in Type 2 Diabetes Mellitus (T2D) and together contribute to the early onset of non‐alcoholic fatty liver disease (NAFLD). Together they lead to overproduction of reactive oxygen species (ROS)‐ induced oxidative stress, which is considered to be a key mechanism in the development of NAFLD. However, current diabetic therapeutic strategies have failed to halt hepatic oxidative stress efficiently, indicating that anti‐oxidant therapeutic research is needed. Recent studies from our laboratory have demonstrated that Ellagic Acid (EA), a naturally occurring polyphenol found in berries and nuts, possesses an anti‐oxidant effect in the vasculature of diabetic rats. Based on these previous findings, we hypothesize that EA improves hepatic oxidative stress and insulin resistance in type 2 diabetic rats. To test our hypothesis, we utilized adult female Goto Kakizaki (GK) rats, a non‐obese, spontaneous model of T2D. GK rats were randomized into two groups: The experimental group received 50 mg/kg of EA via gavage daily for six weeks compared to the control group which was treated with a placebo vehicle. After euthanasia with isoflurane (via nasal 5% in 100% O2), blood and liver samples were collected. Strikingly, we found that while EA treatment decreased the fasting blood glucose of GK rats (109 ± 3.674 vs. 139.3 ± 10.35 in control, p&lt;0.05), there was no significant difference in the fasting triglyceride levels (33.7 ± 4.27 vs. 38.52 ± 5.785 in control). Using dihydroethidium (DHE) staining, we found that treatment with EA reduced levels of oxidative stress in the liver of diabetic rats (Figure 1), confirming that the anti‐oxidant effect of EA is also implicated in the liver. Moreover, EA treatment had a 21.8% reduction in the HOMA‐IR value, indicating decreased insulin resistance (Figure 2). Next, we evaluated the effect of EA in the activation of Akt, a key molecule in the insulin signaling pathway. Levels of phosphorylated Akt (Serine 473), an active Akt form, were increased in hepatic tissues after treatment with EA (2.4 fold increase vs. control, p&lt;0.05). We also found that NF‐E2‐related factor‐2 (Nrf‐2), a crucial transcriptional factor that regulates antioxidant mechanisms, was upregulated in the livers of diabetic rats treated with EA (1.8 fold increase vs. control, p&lt;0.05). Collectively, our findings indicate that EA ameliorates insulin sensitivity and hepatic oxidative stress via Akt/Nrf‐2 signaling pathway activation. In conclusion, these results support EA as a potential adjunctive treatment in T2D, given the ability to halt oxidative damage and potentially inhibit the development of NAFLD.Support or Funding InformationIn‐house grant: New York Institute of Technology College of Osteopathic MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Renal outcomes with sodium glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, in obese insulin-resistant model

A growing body of evidence indicates that obesity and insulin resistance contribute to the progression of renal disease. This study was performed to determine the effects of dapagliflozin, a novel sodium glucose cotransporter 2 (SGLT2) inhibitor, on renal and renal organic anion transporter 3 (Oat3) functions in high-fat diet fed rats, a model of obese insulin-resistance. Twenty-four male Wistar rats were divided into two groups, and received either a normal diet (ND) (n = 6) or a high-fat diet (HFD) (n = 18) for 16 weeks. At week 17, the HFD-fed rats were subdivided into three subgroups (n = 6/subgroup) and received either a vehicle (HFD), dapagliflozin (HFDAP; 1.0 mg/kg/day) or metformin (HFMET; 30 mg/kg/day), by oral gavage for four weeks. Metabolic parameters, renal function, renal Oat3 function, renal oxidative stress, and renal morphology were determined. The results showed that obese insulin-resistant rats induced by HFD feeding had impaired renal function and renal Oat3 function together with increased renal oxidative injury. Dapagliflozin or metformin treatment decreased insulin resistance, hypercholesterolemia, creatinine clearance and renal oxidative stress leading to improved renal function. However, dapagliflozin treatment decreased blood pressure, serum creatinine, urinary microalbumin and increased glucose excretions, and showed a greater ability to ameliorate impaired renal insulin signaling and glomerular barrier damage than metformin. These data suggest that dapagliflozin had greater efficacy than metformin for attenuating renal dysfunction and improving renal Oat3 function, at least in part by reducing renal oxidative stress and modulating renal insulin signaling pathways, and hence ameliorating renal injury.

Effect of oral vitamin D supplementation on glycemic control in patients with type 2 diabetes mellitus with coexisting hypovitaminosis D: A parellel group placebo controlled randomized controlled pilot study

ContextVitamin D supplementation in type 2 diabetes mellitus patients may lead to improved glycemic control by improving insulin secretion and decreasing insulin resistance. AimsTo investigate effect of oral vitamin D supplementation on glycemic control, in patients with type 2 diabetes mellitus and coexisting hypovitaminosis D. Settings and designRandomized, Parallel Group, Placebo Controlled Trial carried out in a tertiary care hospital of Indian Armed Forces. Methods and materialSixty patients with coexisting type 2 diabetes mellitus and hypovitaminosis D were randomized into cases and controls and were supplemented with oral Vitamin D and microcrystalline cellulose respectively for six months. Subjects' HbA1c and vitamin D levels were monitored at the beginning and end of the study, fasting plasma glucose (FPG) & post prandial plasma glucose (PPPG) during monthly OPD visits. Statistical analysis usedIntra-group comparison was made by paired t test & unpaired t test was used for inter-group (A v/s B) comparisons. Repeated measures ANOVA was undertaken to compare values over time. ResultsThe two groups were comparable for all parameters at baseline. Case group showed significant decrease in mean HbA1c levels (7.29% to 7.02%; P = 0.01), mean FPG levels (131.4 to 102.6 mg/dl; P = 0.04) and mean PPPG levels (196.2 to 135.0 mg/dl; P < 0.001). Incidentally, significant improvement in systolic as well as diastolic blood pressure and total cholesterol was also noted in the cases, while for LDL cholesterol improvement tended towards significance (p = 0.05). ConclusionsWe found that oral vitamin D supplementation was associated with improved glycemic control and other metabolic parameters in patients with type 2 diabetes mellitus. Supplementation to achieve normal levels of vitamin D can be a promising adjuvant therapy for T2DM patients & coexisting hypovitaminosis D.

The significance of anthocyanins in the prevention and treatment of type 2 diabetes.

Anthocyanins are food compounds which belong to polyphenols and can mainly be found in dark fruits (e.g., blueberries, black currants, cranberries) and vegetables (e.g., red cabbage, radish, eggplant). The results of large research have shown that these compounds play an important role in the prevention of type 2 diabetes (T2D). In rodent studies and in studies with isolated omental adipocytes, it was observed that anthocyanins regulated the carbohydrate metabolism in the body due to the upregulation of GLUT4 (insulinregulated glucose transporter) translocation, increased activation of PPARγ (peroxisome proliferator-activated receptor-γ) in adipose tissue and skeletal muscles as well as increased secretion of adiponectin and leptin. Moreover, these compounds reduced the inflammation status in the body. Studies conducted on humans and experimental animals showed that anthocyanins decrease insulin resistance. This effect may be achieved by the upregulation of GLUT4 gene expression, activation of AMP-activated protein kinase and downregulation of retinol binding protein 4 (RBP4) expression. Anthocyanins also increased the uptake and utilization of glucose by tissues in streptozotocin-induced diabetic rats and mice, and they also protected pancreatic cells against necrosis induced by streptozotocin. Another mechanism that might explain the lower glucose level in the blood after a meal with anthocyanins compared to a meal without them is the inhibition of intestinal α-glucosidase and pancreatic α-amylase by these compounds. Moreover, anthocyanins improve insulin secretion, which can have a special meaning for people with T2D. The evidence from the presented studies suggests that foods rich in anthocyanins may be one of the diet elements supporting the prevention and treatment of T2D.

Effect of Diabetes Sleep Education for T2DM Who Sleep After Midnight: A Pilot Study from China.

Our prior study showed that patients with sleep disorders had poor blood pressure (BP), glycemic control, and more severe complications. Therefore, sleep is very important for diabetic control. Our work was to investigate whether individualized diabetes sleep education significantly improve sleep quality and glycemic control in type 2 diabetic patients who sleep after midnight and potential mechanism by a randomized parallel interventional study. T2D patients were randomly recruited to an intervention or control group. Patients received structured special diabetes sleep education program with 3-month follow-up. Pittsburg Sleep Quality Index (PSQI) was scored for each participant. Demographic data, HbA1c, biochemical, and some hormones were also examined. SPSS 13.0 was used for statistical analysis. One hundred patients were approached, and 45 were enrolled into our trial. Eventually, 31 patients completed the study. Patients in the intervention group greatly improved their sleep hygiene. After intervention, PSQI scores were lowered significantly (-1.48 ± 0.88 vs. -0.51 ± 0.71, P < 0.001), as well as significant reduction of HbA1c (-1.5 ± 0.55 vs. -1.11 ± 0.47, P < 0.05). Fasting plasma glucose was also lowered significantly. Homeostasis model assessment of insulin resistance was reduced significantly (-1.29 ± 0.97 vs. 1.04 ± 0.91, P < 0.01). Serum concentrations for interleukin (IL)-6, cortisol, and ghrelin were decreased significantly. Ghrelin (coefficients -0.65, P < 0.001), cortisol (coefficients -0.38, P < 0.05), and IL-6 (coefficients 0.452, P < 0.05) were correlated with HbA1c improvement. The change of ghrelin was negatively associated with the improvement of HbA1c. Diabetes sleep education could improve sleep quality, better blood glucose and BP, and decrease insulin resistance through healthier sleep hygiene. Lower serum concentration of ghrelin might be partly involved in the reduction of HbA1c.

IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice

Background and ObjectiveInterleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus. MethodsTwelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed. ResultsDb/db mice treated with Tocilizumab exhibited reduced proteinuria and glomerular mesangial matrix accumulation compared to db/db + IgG controls. Additionally, Tocilizumab suppressed inflammatory response, oxidative stress and the IL-6 signaling pathway in the diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the activation of NLRP3 inflammasome partly through inhibition of IL-17A. Furthermore, insulin resistance assessed by glucose tolerance test, was ameliorated by Tocilizumab treatment. ConclusionsThe protective effects of an IL-6 receptor blockade against diabetic renal injury may be due to decreased insulin resistance and inhibition of the inflammasome.

Triiodothyronine improves age-induced glucose intolerance and increases the expression of sirtuin-1 and glucose transporter-4 in skeletal muscle of aged rats.

To evaluate the potential beneficial impact and to clarify the underlying mechanisms of triiodothyronine (T3) on glucose intolerance in aged rats. Rats were divided into adult group, aged group, and T3-treated aged group (T3-aged). T3 was administered at a dose of 8 µg/kg body weight for 2 weeks. In comparison to adult group, aged rats presented significant higher levels of fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Glucose area under the curve (AUC), and peak glycemia, estimated from oral glucose tolerance curve, were significantly increased along with decreased mRNA expression of skeletal muscle sirtuin-1, glucose transporter-4 (GLUT-4) and uncoupling protein-3 (UCP-3) in aged versus adult group. T3 administration significantly decreased the serum levels of fasting insulin, HOMA-IR, glucose AUC, and peak glycemia in T3-aged versus aged rats. Skeletal muscle mRNA expression of sirtuin-1 and GLUT-4 were increased, whereas UCP-3 was not changed by T3 administration. T3 administration improved glucose intolerance, and decreased insulin resistance in aged rats. This was associated with upregulation of skeletal muscle sirtuin-1 and GLUT-4 which could mediate such beneficial effect.