Differences In Insulin Levels Research Articles

Proposal for fasting insulin and HOMA-IR reference intervals based on an extensive Brazilian laboratory database.

Fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) index are relatively simple and reliable noninvasive markers of insulin resistance (IR). Given the relevance of correctly diagnosing IR, we emphasize the importance of establishing reliable reference intervals (RIs) for these markers. This study aimed to determine the RIs of fasting insulin and HOMA-IR index in adults living in Rio de Janeiro and, secondarily, to verify potential RI differences between sexes. Serum insulin levels of 146,497 individuals (ages 20-60 years) who underwent blood sampling in the state of Rio de Janeiro were obtained retrospectively through access to an extensive laboratory database. Insulin was measured using the electrochemiluminescence immunoassay method. After applying exclusion criteria, 21,684 individuals (18,576 [86%] women) were included. The RIs were estimated using a computational mining approach that integrates a selection of R packages. The 95% RIs in women and men and in the overall population were, respectively, 2.54-13.30 μU/mL (15.3-80.12 pmol/L), 2.43-11.89 μU/mL (14.6-71.7 pmol/L), and 2.52-13.14 μU/mL (15.2-79.2 pmol/L) for fasting insulin levels and 0.39-2.86, 0.38-2.81, and 0.39-2.86 for HOMA-IR values. Despite significant differences in insulin levels and HOMA-IR index between men and women, the use of sex-specific RIs was not justified. The RIs of fasting insulin levels and HOMA-IR values found in the overall population can be applied to both sexes. Thus, for our population, we suggest the RIs of 2.52-13.14 μU/mL (15.1-78.8 pmol/L) for fasting insulin and 0.39-2.86 for the HOMA-IR index.

Impaired Incretin Homeostasis in Nondiabetic Moderate-to-Severe CKD.

Key Points Total incretin levels and incretin response during oral glucose tolerance testing were significantly higher among patients with moderate-to-severe nondiabetic patients with CKD compared with healthy people.Unlike in healthy individuals, increased incretin response was not correlated with insulin response and coincided with persistently greater glucagon levels to oral glucose tolerance testing in CKD.Disruption in the incretin system and glucagon dynamics may contribute to metabolic complications in moderate-to-severe CKD. Background Incretins are regulators of insulin secretion and glucose homeostasis metabolized by dipeptidyl peptidase-4 (DPP-4). CKD may modify incretin release, metabolism, or response. Methods We performed 2-hour oral glucose tolerance testing in 59 people with nondiabetic CKD (eGFR <60 ml/min per 1.73 m2) and 39 matched controls. We measured total area under the curve and incremental area under the curve (iAUC) of plasma total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic polypeptide (GIP). Fasting DPP-4 levels and activity were measured. Linear regression was used to adjust for demographic, body composition, and lifestyle factors. Results Mean (SD) eGFR was 38±13 and 89±17 ml/min per 1.73 m2 in patients with CKD and controls, respectively. GLP-1 total area under the curve and GIP iAUC were higher in patients with CKD than controls with a mean of 1531±1452 versus 1364±1484 pM×min and 62,370±33,453 versus 42,365±25,061 pg×min/ml, respectively. After adjustment, CKD was associated with 15,271 pM×min/ml greater GIP iAUC (95% confidence intervals [CIs], 387 to 30,154) compared with controls. Adjustment for covariates attenuated associations of CKD with higher GLP-1 iAUC (adjusted difference, 122; 95% CI, −619 to 864). Plasma glucagon levels were higher at 30 minutes (mean difference, 1.6; 95% CI, 0.3 to 2.8 mg/dl) and 120 minutes (mean difference, 0.84; 95% CI, 0.2 to 1.5 mg/dl) in patients with CKD compared with controls. There were no differences in insulin levels or plasma DPP-4 activity or levels between groups. Conclusions Overall, incretin response to oral glucose is preserved or augmented in moderate-to-severe CKD, without apparent differences in circulating DPP-4 concentration or activity. However, neither insulin secretion nor glucagon suppression is enhanced.

Essential Improvements in Fat Percentage and Cardiometabolic Fitness After a Residential Stay for Socially Vulnerable Children-With and Without the "11 for Health" Concept.

The Danish Christmas Seal Homes offer a 10-week residential stay for socially vulnerable children. We aimed to examine the effects on body composition and cardiometabolic fitness variables of the standard program (SG) and whether substituting physical activity sessions with sessions from a football-based health education program is beneficial for the participants ("11 for Health"; SG+). Three hundred and nine children participated in SG (12.4 [1.6]y) and 305 in SG+ (12.4 [1.4]y). Fat percentage was lowered by 6% for females (from 37% to 31%) and 8% for males (from 36% to 28%), with no between-group differences. We observed improvements in systolic and diastolic blood pressure (3 and 5mm Hg, respectively), resting heart rate (10beats/min), aerobic fitness, jump performance, and relative muscle mass with no between-group differences. Furthermore, there were between-group differences in insulin levels for females (1.7 pmol/L; 95% CI, 0.3 to 3.0) and postural balance for males (1.0s; 95% CI, 0.0 to 2.0), both in favor of SG+, and covered distance in the Andersen test for females (26m; 95% CI, 3 to 49) in favor of SG. In conclusion, a 10-week stay at the Danish Christmas Seal Home resulted in clinically relevant improvement in fat percentage and cardiometabolic fitness in socially vulnerable children, regardless of the program type.

Increased Plasma Branched Short-Chain Fatty Acids and Improved Glucose Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Short chain fatty acids (SCFA) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched short chain fatty acids (BSCFA), isobutyrate, isovalerate, and methylbutyrate, is largely unknown. In a cohort of 219 non-Hispanic Whites and 126 African Americans, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, lipid traits, and other SCFA. We observed a bimodal distribution of BSCFA, with 25 individuals having high levels (HBSCFA group) and 320 individuals having lower levels (L-BSCFA group). The prevalence of dysglycemia was lower in the H-BSCFA group compared to the L-BSCFA group (16% versus 49%, P=0.0014). This association remained significant after adjustment for age, sex, race, BMI, and levels of other SCFA. Consistent with the lower rate of dysglycemia, fasting and postprandial glucose were lower and disposition index was higher in the H-BSCFA group. Additional findings in H-BSCFA versus L-BSCFA included lower fasting and postprandial Cpeptide levels and lower insulin clearance without differences in insulin levels, insulin sensitivity, insulin secretion, or other variables examined, including diet and physical activity. As one of the first human studies associating higher BSCFA levels with lower odds of dysglycemia and improved glucose homeostasis, this study sets the stage for further investigation of BSCFA as a novel target for prevention or treatment of diabetes.

Effects of green coffee aqueous extract supplementation on glycemic indices, lipid profile, CRP, and malondialdehyde in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial.

Studies have reported the health benefits of green coffee extract (GCE) in experimental models. In the current study, we aimed to determine whether supplementation with GCE improves glycemic indices, inflammation, and oxidative stress in patients with type 2 diabetes (T2D). This randomized, double-blind, placebo-controlled trial included 44 patients (26 male and 18 female) with T2D and overweight/obesity. After blocked randomization, patients received either capsules containing 400 mg GCE twice per day (n = 22) or a placebo (n = 22) and were followed for 10 weeks. In this study, glycemic indices, lipid profiles, anthropometric examinations, blood pressure, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured twice; at baseline and at the end of the study. After 10 weeks of supplementation, GCE supplementation significantly reduced body weight (p = 0.04) and body mass index (BMI) (p = 0.03) compared to the placebo. The intention-to-treat (ITT) analysis indicated patients in the GCE group had a lower fasting blood glucose (FBG) concentration compared to the placebo group; however, this decreasing was marginally significant (8.48 ± 8.41 vs. 1.70 ± 5.82 mg/dL, p = 0.05). There was no significant difference in insulin levels and HOMA-IR between the groups. At the end of the study, significant changes in systolic blood pressure (SBP) (p = 0.01), triglyceride (TG) level (p = 0.02), high-density lipoprotein (HDL) (p = 0.001), and TG-to-HDL ratio (p = 0.001) were found between the intervention and placebo groups. Our trial indicated GCE supplementation had no effect on diastolic blood pressure (DBP), low-density lipoprotein (LDL), or total cholesterol. During the supplementation period, the hs-CRP level significantly decreased in the GCE group compared to the placebo group (p = 0.02). No significant changes were observed in the MDA level between the two groups at the end of the study (p = 0.54). Our findings showed beneficial effects of GCE on SBP, TG, hs-CRP, and HDL levels in patients with T2D and overweight/obesity over a 10-week period of supplementation.Clinical trial registration:https://en.irct.ir/trial/48549, identifier [IRCT20090203001640N18].

Anthropometry and blood biomarkers of diabetes and their possible association with obesity and metabolic syndrome.

Diabetes, a rapidly increasing heterogeneous disorder, is closely linked to the epidemic of obesity and metabolic syndrome (MetS). At present, we do not understand completely the blood biomarkers, molecular aetiology, and role of lifestyle modification and interventions to combat diabetes hand in hand with obesity and the MetS epidemic. To measure different anthropometric and blood biomarkers in pre-diabetic and diabetic patients, we collected data and blood samples from patients in a hospital OPD. This was a cross-sectional study that included the identification of possible relationships between different parameters to predict early diagnostic markers of diabetes. We found increased body mass index (BMI), fasting blood glucose, neck, waist, and hip circumference, sagittal abdominal diameter, and skin fold thickness in the diabetic as compared to the pre-diabetic group. Also, serum uric acid and insulin resistance (HOMA-IR) values were significantly increased in diabetic individuals. We found a significant positive correlation between serum uric acid and BMI, fasting blood glucose, serum insulin, and HOMA-IR values. Here, we found that pre-diabetic and diabetic patients have increased fasting glucose levels while we did not find any difference in insulin levels. Both pre-diabetic and diabetic patients show high serum uric acid, positively associated with a higher prevalence of diabetes and HOMA-IR. Uric acid may hence be an important parameter for early diagnostics. These findings may be used as a basis for future studies that aim to identify the mechanistic details of the association of uric acid with insulin signaling and hence better understanding of the phenomenon associated with diabetes. The online version contains supplementary material available at 10.1007/s40200-023-01276-4.

THU302 Protective Effects Of Lactation On Maternal Metabolism

Abstract Disclosure: J.R. Hens: None. Y. Ding: None. S. Brown: None. H. Song: None. J.J. Wysolmerski: None. R. Belfort De Aguiar: None. A history of lactation significantly lowers the risk of developing Type 2 diabetes (T2D) by almost 50%. However, little is known about how milk production durably changes maternal metabolism. We hypothesized that lactation protects against diabetes by improving maternal glucose metabolism. Changes in body composition, glucose metabolism, insulin secretion and tissue triglyceride levels were measured in age-matched cohorts of mice that lactated (L) or did not lactate but went through a pregnancy (NL); age-matched virgins served as controls (V). L and NL mice were studied 4 weeks after weaning of pups from the L group. An euglycemic-hyperinsulinemic clamp was used to further examine glucose metabolism. Multiple rounds of lactation were examined to determine if body composition or glucose metabolism changed with repeated cycles of reproduction. Liver weight was higher in L mice when compared to V mice. Liver triglycerides were lower in L and NL mice when compared to V mice. Circulating fasting levels of plasma free fatty acids were unchanged between the three groups. Perigonadal fat trended higher in NL mice compared to L and V mice after one round of lactation. However, after two rounds of lactation, NL mice had significantly more perigonadal fat than L or V mice. Fasting glucose trended lower in L mice compared to NL mice, but there was no difference in insulin levels between groups. The area under the curve of glucose tolerance test was not different between groups. Pancreases from L mice had increased numbers of islets compared to NL and V mice. Insulin action was assessed in chow-fed, conscious, unrestrained L, NL, and V mice using the euglycemic-hyperinsulinemic clamp technique. Tail-vein glucose was clamped at 100-120 mg/dL. The normalized glucose infusion rate to insulin was significantly lower (p=0.01) in NL mice (41.9 +/- 17) compared to V mice (91.8 +/- 14 and L mice (83.8 +/- 27). Our results suggest that pregnancy and lactation significantly alter the metabolic functions of liver, adipose, muscle, and pancreas. Furthermore, a history of lactation improves insulin sensitivity in parous mice. Further study of the metabolic changes occurring during lactation may have wide-ranging implications for women’s health. Presentation: Thursday, June 15, 2023

Role of Melatonin in Daily Variations of Plasma Insulin Level and Pancreatic Clock Gene Expression in Chick Exposed to Monochromatic Light.

To clarify the effect of monochromatic light on circadian rhythms of plasma insulin level and pancreatic clock gene expression and its mechanism, 216 newly hatched chicks were divided into three groups (intact, sham operation and pinealectomy) and were raised under white (WL), red (RL), green (GL) or blue (BL) light for 21 days. Their plasma and pancreas were sampled at six four-hour intervals. For circadian rhythm analysis, measurements of plasma melatonin, insulin, and clock gene expression (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2, and cPer3) were made. Plasma melatonin, insulin, and the pancreatic clock gene all expressed rhythmically in the presence of monochromatic light. Red light reduced the mesor and amplitude of plasma melatonin in comparison to green light. The mesor and amplitude of the pancreatic clock gene in chickens exposed to red light were dramatically reduced, which is consistent with the drop in plasma melatonin levels. Red light, on the other hand, clearly raised the level of plasma insulin via raising the expression of cVamp2, but not cInsulin. After the pineal gland was removed, the circadian expressions of plasma melatonin and pancreatic clock gene were significantly reduced, but the plasma insulin level and the pancreatic cVamp2 expression were obviously increased, resulting in the disappearance of differences in insulin level and cVamp2 expression in the monochromatic light groups. Therefore, we hypothesize that melatonin may be crucial in the effect of monochromatic light on the circadian rhythm of plasma insulin level by influencing the expression of clock gene in chicken pancreas.

RF04 | PSUN297 Genetic Knockout of Intestinal Hexokinase Domain Containing Protein-1 Affects Enterocyte Glucose Transport in Mice Fed High Fat Diet

Abstract Hexokinase domain containing protein-1, or HKDC1, is a widely expressed novel hexokinase that is genetically associated with elevated 2-hour gestational blood glucose levels during an oral glucose tolerance test, suggesting a role for HKDC1 in postprandial glucose regulation during pregnancy. Our earlier studies utilizing transgenic mice containing whole-body HKDC1 knockdown, or mice in which hepatic HKDC1 was overexpressed or knocked out, indicated that HKDC1 is important for whole-body glucose homeostasis in aging and pregnancy, through modulation of glucose tolerance, peripheral tissue glucose utilization, and hepatic energy storage. However, our knowledge of the precise mechanisms by which HKDC1 regulates postprandial glucose homeostasis under normal and diabetic conditions is lacking. As the intestine is the main entry portal for dietary glucose, and since HKDC1 is highly expressed within the intestine, in this study we assessed and characterized the in vivo significance of intestine-specific HKDC1 in regulating glucose homeostasis under normal and obesogenic conditions. We developed an intestine-specific HKDC1 knockout mouse model, HKDC1Int-/-, utilizing Cre-mediated recombination of HKDC1 in which Cre was expressed under the control of the villin gene promoter, leading to genetic knockout of HKDC1 solely within the intestinal epithelium. Mice were maintained until 28 weeks of age on either a normal chow diet or a high fat diet to develop obesity, hyperglycemia, and insulin resistance. While no overt glycemic phenotype was observed, 28-week-old HKDC1Int-/- mice fed a high fat diet exhibited an increased glucose excursion following an oral glucose load compared to mice expressing intestinal HKDC1. This finding was not due to differences in insulin levels, whole-body insulin tolerance, or gluconeogenesis, nor was it a result of alterations in enterocyte glucose utilization or a reduction in peripheral skeletal muscle glucose uptake. Furthermore, the enhanced glucose excursion was related to transport of glucose through the intestinal epithelium, as mice administered an intraperitoneal glucose load did not exhibit alterations in post-load glycemic excursion. Assessment of intestinal glucose transporters in high fat diet-fed HKDC1Int-/- mice indicated an increased expression of GLUT2 in the enterocyte apical membrane in the fasting state. Taken together, our results indicate that intestine-specific HKDC1 contributes to postprandial glycemic regulation by modulating dietary glucose transport across the intestinal epithelium under conditions of enhanced metabolic stress, such as obesity, hyperglycemia, and diabetes. Presentation: Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Association of GLP1R Polymorphisms With the Incretin Response.

Polymorphisms in the gene encoding the glucagon-like peptide-1 receptor (GLP1R) are associated with type 2 diabetes but their effects on incretin levels remain unclear. We evaluated the physiologic and hormonal effects of GLP1R genotypes before and after interventions that influence glucose physiology. Pharmacogenetic study conducted at 3 academic centers in Boston, Massachusetts. A total of 868 antidiabetic drug-naïve participants with type 2 diabetes or at risk for developing diabetes. We analyzed 5 variants within GLP1R (rs761387, rs10305423, rs10305441, rs742762, and rs10305492) and recorded biochemical data during a 5-mg glipizide challenge and a 75-g oral glucose tolerance test (OGTT) following 4 doses of metformin 500 mg over 2 days. We used an additive mixed-effects model to evaluate the association of these variants with glucose, insulin, and incretin levels over multiple timepoints during the OGTT. During the OGTT, the G-risk allele at rs761387 was associated with higher total GLP-1 (2.61 pmol/L; 95% CI, 1.0.72-4.50), active GLP-1 (2.61 pmol/L; 95% CI, 0.04-5.18), and a trend toward higher glucose (3.63; 95% CI, -0.16 to 7.42 mg/dL) per allele but was not associated with insulin. During the glipizide challenge, the G allele was associated with higher insulin levels per allele (2.01 IU/mL; 95% CI, 0.26-3.76). The other variants were not associated with any of the outcomes tested. GLP1R variation is associated with differences in GLP-1 levels following an OGTT load despite no differences in insulin levels, highlighting altered incretin signaling as a potential mechanism by which GLP1R variation affects T2D risk.

Enterocyte HKDC1 Modulates Intestinal Glucose Absorption in Male Mice Fed a High-fat Diet.

Hexokinase domain containing protein-1, or HKDC1, is a widely expressed hexokinase that is genetically associated with elevated 2-hour gestational blood glucose levels during an oral glucose tolerance test, suggesting a role for HKDC1 in postprandial glucose regulation during pregnancy. Our earlier studies utilizing mice containing global HKDC1 knockdown, as well as hepatic HKDC1 overexpression and knockout, indicated that HKDC1 is important for whole-body glucose homeostasis in aging and pregnancy, through modulation of glucose tolerance, peripheral tissue glucose utilization, and hepatic energy storage. However, our knowledge of the precise role(s) of HKDC1 in regulating postprandial glucose homeostasis under normal and diabetic conditions is lacking. Since the intestine is the main entry portal for dietary glucose, here we have developed an intestine-specific HKDC1 knockout mouse model, HKDC1Int–/–, to determine the in vivo role of intestinal HKDC1 in regulating glucose homeostasis. While no overt glycemic phenotype was observed, aged HKDC1Int–/– mice fed a high-fat diet exhibited an increased glucose excursion following an oral glucose load compared with mice expressing intestinal HKDC1. This finding resulted from glucose entry via the intestinal epithelium and is not due to differences in insulin levels, enterocyte glucose utilization, or reduction in peripheral skeletal muscle glucose uptake. Assessment of intestinal glucose transporters in high-fat diet–fed HKDC1Int–/– mice suggested increased apical GLUT2 expression in the fasting state. Taken together, our results indicate that intestinal HKDC1 contributes to the modulation of postprandial dietary glucose transport across the intestinal epithelium under conditions of enhanced metabolic stress, such as high-fat diet.

Short-term Western-style diet negatively impacts reproductive outcomes in primates.

A maternal Western-style diet (WSD) is associated with poor reproductive outcomes, but whether this is from the diet itself or underlying metabolic dysfunction is unknown. Here, we performed a longitudinal study using regularly cycling female rhesus macaques (n = 10) that underwent 2 consecutive in vitro fertilization (IVF) cycles, one while consuming a low-fat diet and another 6–8 months after consuming a high-fat WSD. Metabolic data were collected from the females prior to each IVF cycle. Follicular fluid (FF) and oocytes were assessed for cytokine/steroid levels and IVF potential, respectively. Although transition to a WSD led to weight gain and increased body fat, no difference in insulin levels was observed. A significant decrease in IL-1RA concentration and the ratio of cortisol/cortisone was detected in FF after WSD intake. Despite an increased probability of isolating mature oocytes, a 44% reduction in blastocyst number was observed with WSD consumption, and time-lapse imaging revealed delayed mitotic timing and multipolar divisions. RNA sequencing of blastocysts demonstrated dysregulation of genes involved in RNA binding, protein channel activity, mitochondrial function and pluripotency versus cell differentiation after WSD consumption. Thus, short-term WSD consumption promotes a proinflammatory intrafollicular microenvironment that is associated with impaired preimplantation development in the absence of large-scale metabolic changes.

Comparison of the effects of laparoscopic sleeve gastrectomy in adults and adolescents

Background: Obesity is an increasing problem worldwide regardless of age. Bariatric surgery is highly effective both in the treatment of obesity and in the improvement of obesity-related comorbidities. Laparoscopic sleeve gastrectomy is gaining popularity in both adolescents and the elderly.Methods: A total of 64 patients who underwent laparoscopic sleeve gastrectomy, aged under 19 and older 65 between March 2013 and December 2019 were enrolled in this retrospective study. Demographic characteristics were recorded in all patients.Results: Between March 2013 and December 2019, 64 patients who underwent laparoscopic sleeve gastrectomy were enrolled in this study. Fourty-five patients were smaller than 19 years old and 19 patients were older than 65 years old. After 1-year follow-up, there was a significant improvement in glucose, insulin level, excess weight loss and body mass index in both groups (p<0.001). There was no significant difference in insulin levels (p=0.2) and body mass index (p=0.94) between two groups.Conclusions: Careful patient selection after adequate risk versus benefit evaluation by an expert multidisciplinary team is essential. Laparoscopic sleeve gastrectomy is an effective treatment for obesity and its related comorbidities in both adolescents and adults.

Oral Recombinant Methioninase Inhibits Diabetes Onset in Mice on a High-fat Diet.

We have recently shown that oral recombinant methionase (o-rMETase) prevents obesity in mice on a high-fat (HF) diet. The present study aimed to determine if o-rMETase can inhibit the onset of diabetes in mice on a HF diet. The mice on a HF diet were divided into two groups: 1) HF+phosphate buffered saline (PBS) group; 2) HF+o-rMETase group. The blood glucose level in the HF+PBS group increased to average of 201 mg/dl during the experimental period of 8 weeks. In contrast, the blood glucose level in the HF+o-rMETase group maintained an average of 126 mg/dl (p<0.01, HF+PBS vs. HF+o-rMETase). The glucose tolerance test showed a significant increase in tolerance in the HF+o-rMETase group at 120 min after glucose injection compared to the HF+PBS group (p=0.04). Visceral adipose tissue was significantly less in the HF+o-rMETase group than the HF+PBS group (p=0.05). There was no difference in insulin levels, cholesterol or triglycerides between the HF+PBS and HF+o-rMETase groups. o-rMETase inhibited the onset of diabetes as well as prevented obesity on a high-fat diet, offering a possibility of a new and easy-to-use alternative to severe dieting or insulin injections.

The Effect of Resveratrol Supplementation on Cardio-Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized, Double-Blind Controlled Trial.

The aim of the present randomized controlled trial was to evaluate the effect of a micronized resveratrol supplement on glycemic status, lipid profile, and body composition in patients with type 2 diabetes mellitus (T2DM). A total of 71 overweight patients with T2DM (body mass index ranged 25-30) were randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Anthropometric indices and biochemical indices including lipid and glycemic profile were measured before and after the intervention. In adjusted model (age, sex, and baseline body mass index), resveratrol decreased fasting blood sugar (-7.97±13.6 mg/dL, p=0.05) and increased high density lipoprotein (3.62±8.75 mg/dL, p=0.01) levels compared with placebo. Moreover, the mean difference in insulin levels reached significance (-0.97±1.91, μIU/mL, p= 0.02). However, no significant differences were observed for anthropometric measures. It was found that 8-week resveratrol supplementation produced useful effects on some cardio-metabolic parameters in patients with T2DM. More studies are needed to confirm these findings.

The effect of Leaf Salam Extracts (Syzygium polyanthum) in diabetes mellitus therapy on wistar albino rats

Diabetes mellitus (DM) is one of the chronic disease that caused the most complications and even death. Non-Insulin Dependent Diabetes Mellitus (NIDDM) is the most widely recognized. It is closely related with the incidence of insulin resistance. This research is an in vivo experimental study with post-test control group design located in laboratory of animal house and biomolecular laboratory Faculty of Medicine, Universitas Sriwijaya, Indonesia. The subjects of this study were albino rats (Rattus norvegicus), Wistar strain, divided into 5 groups are negative control, positive control (TZD), Leaf Salam Extract (LSE) 50 mg/kgBW, 100 mg/kgBW and 200 mg/kgBW. Rat was injected by Human Insulin (ip) 1,8 IU/kgBW and orally glucose for 14 days. In this study it was found that there was no distinction in blood sugar levels in the positive control group with LSE 200 mg/kgBW, LSE 100 mg/kgBW and LSE 50 mg/kgBW and there were no difference in insulin levels in the positive control group with LSE 200 mg/kgBW and LSE 100 mg/kgBW and LSE 50 mg/kgBW. So, it can be concluded that LSE (Syzygium polyanthum) was effective in lowering blood sugar and insulin levels of Wistar albino rat induced diabetes mellitus.

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.

PENGARUH PEMBERIAN VITAMIN C, VITAMIN E, DAN KROMIUM (CR3+) TERHADAP KADAR INSULIN TIKUS WISTAR YANG DIINDUKSI ALOKSAN

Objective: To analyze the effect of vitamin C, vitamin E, and chromium (Cr3+) on insulin levels Wistar ratswere induced alloxan.Materials and Methods: This study is an experimental laboratory. Using rats typeWistar strain Rattus novergicus for 6 weeks with a number of 20 head. The independent variables consist of 5treatment groups namely normal diet, normal diet + 1 g/hr chromium, normal diet + 2 mg/day of vitamin C,normal diet + 0.5 mg/day of vitamin E, normal diet + 1 g/hr chromium + 2 mg/day of vitamin C + 0.5mg/day of vitamin E. The dependent variable is the level of insulin. To know the differences of eachtreatment used statistical tests One Way ANOVA, followed by Tukey HSD Post Hoc test withp&lt;0.05.Results: There were significant differences in insulin levels (p&lt;0.05) in the control group, 1, 2, and 4.But in the control group and the group 3 there are no significant differences in insulin levels (p=0.145).Conclusion: Delivery of chromium (treatment 1), vitamin C (treatment 2), and a mixture of chromium,vitamin C, vitamin E (treatment 4) effect on insulin levels, while administration of vitamin E (treatment 3)alone had no effect on insulin levels

The role of nitric oxide in obstructive sleep apnea-induced insulin resistance

Background: Insulin resistance (IR) is a characteristic feature in patients who are developing Type 2 diabetes in the prediabetic stage. Obstructive sleep apnea (OSA) is a breathing disorder characterized by frequent episodes of reduced airflow due to obstruction in the upper airway while sleeping. OSA is associated with intermittent hypoxia and predisposition to increased IR. Aims and Objectives: This study investigates the extent of IR in prediabetics and OSA patients and also compares serum nitric oxide (NO) levels in the three study groups. Materials and Methods: Three groups each comprising of 50 people were selected: Group I - control group; Group II - prediabetic patients; and Group III - OSA patients. Fasting blood glucose, insulin, and NO levels were measured in these subjects and IR calculated. Results: Insulin levels and IR were significantly higher in OSA and prediabetic patients when compared to control subjects. There was no significant difference in insulin levels (P > 0.05) between OSA and prediabetic groups. OSA group had significantly lower level of NO compared to both control and prediabetic groups. Conclusion: High insulin levels and IR in prediabetics indicate that they are prone to develop Type 2 diabetes. The same findings in OSA patients could mean that they are also prone to develop Type 2 diabetes. NO levels are significantly low in OSA patients. Low NO level has been associated with hypoxia; this molecule with its wide array of actions may be involved in glucose homeostasis.

Залежність періопераційної ґлікемії від методів знеболювання при артропластиці кульшового суглоба

Aim.&nbsp;The hip joint arthroplasty has high risk of perioperative hyperglycemia due to stress response and insulin resistance. The analgesia technics differ in terms of provided analgesia and anti-stress protection. The aim of our study was analyzing of blood glucose, insulin and HOMA-index dynamics during perioperative period in patients who underwent total hip arthroplasty according to the anaesthesia and analgesia techniques.&nbsp; Material and Methods.&nbsp;The study included 150 patients undergoing primary total hip joint replacement. &nbsp;We analyzed the dynamics of blood glucose, insulin and HOMA-index in relation to four variants of intraoperative anaesthesia and three variants of postoperative analgesia techniques, pathology type and patients' gender. Tests were taken before and during surgery, as well as at the 1st postoperative day. Results and Discussion.&nbsp;The preoperative glycemia level before surgery among all groups did not differ significantly (р&gt;0,1). In the operating room, after the general anaesthesia administration but before the start of the surgery, the patients demonstrated significant increase in glycemia up to 6,3 mmol/L, and it was significantly higher compared to groups of patients with nerve blocks, paravertebral+caudal anaesthesia and spinal anaesthesia (р&lt;0,01). At the traumatic stage of surgery, glycemia was significantly higher in groups of general anaesthesia and nerve blocks, 6,98 аnd 6,43 mmol/L, respectively. At the 1st postoperative day, the highest level of glycemia was detected in patients receiving systemic opioid analgesia, whose &nbsp;level of glycemia was 0,87 mmol/L higher than the initial value before surgery; in the group of epidural analgesia, this difference was 0,1 mmol/L, and in the group of paravertebral analgesia - 0,42 mmol/L. The analysis of the insulin level , depending on the methods of intraoperative analgesia, revealed the following: the lowest level of insulin at the traumatic stage of the operation in the group of spinal anaesthesia was found to be 2,61 mIU/L higher compared to the level prior to the operation, and the values of this group significantly differed from other groups at this stage of the study (p&lt;0,05). At all other stages of the study, the level of insulin among intraoperative anesthesia groups did not differ significantly (p&gt;0,05). The difference in insulin levels between postoperative analgesia groups at any stage of the study was not statistically significant (p&gt;0,1). In the intraoperative period, there was a decrease in the HOMA index in the group of spinal anesthesia, while in all other groups this rate was gradually increasing. The higher HOMA index was found in patients operated on under general anesthesia, who received systemic opioid anesthesia after surgery. The level of glycemia, insulin and HOMA did not significantly differ in any stage of the study between gender groups and groups by type of pathology: coxarthrosis or fractures (p&gt;0,1). Conclusion.&nbsp;Regional analgesia provides a positive effect on the level of glycemia, insulin secretion and insulin resistance development in patients undergoing hip joint arthroplasty.