Comparison of insulin sensitivity between healthy neonatal foals and horses using minimal model analysis

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· μIU-1 [13.4–28.4]) compared to horses (0.9 L·min-1· μIU-1 [0.5–1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103−14 × 103]) compared to horses (4 × 102 [2 × 102−7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 μIUinsulin2/10·L·mgglucose [1.43–2.68]) compared to horses (3.91 μIU insulin2/10·L·mgglucose [2.57–7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43–116]) compared to foals (23.2% [17.8–42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

OBJECTIVE We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes–associated G allele in the melatonin receptor-1b gene (MTNR1B). RESEARCH DESIGN AND METHODS In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime (“early dinner timing”) and a late condition scheduled 1 h prior to habitual bedtime (“late dinner timing”), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responsesbetween early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method. RESULTS Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. In the late condition, MTNR1B G-allele carriers had lower glucose tolerance than noncarriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint Disposition Index = 0.018). CONCLUSIONS Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects.

The Impact of Rhodiola Rosea On Biomarkers of Diabetes, Inflammation, and Gut Microbiota in a Leptin Receptor-Knockout Mouse Model

Type 2 diabetes is the most prevalent endocrine disease in the world, and recently the gut microbiota have become a potential target for its management. Recent studies have illustrated that this disease may predispose individuals to certain microbiome compositions, and treatments like metformin have been shown to change gut microbiota and their associated metabolic pathways. However, given the limitations and side effects associated with pharmaceuticals currently being used for therapy of diabetes, there is a significant need for alternative treatments. In this study, we investigated the effects of a root extract from Rhodiola rosea in a Leptin receptor knockout (db/db) mouse model of type 2 diabetes. Our previous work showed that Rhodiola rosea had anti-inflammatory and gut microbiome-modulating properties, while extending lifespan in several animal models. In this study, treatment with Rhodiola rosea improved the insulin response, and significantly decreased serum lipopolysaccharide and C-reactive protein levels. We hypothesize that these changes may in part reflect the modulation of the microbiota, resulting in improved gut barrier integrity and decreasing the translocation of inflammatory biomolecules into the bloodstream. These findings indicate that Rhodiola rosea is an attractive candidate for further research in the management of type 2 diabetes.

Effects of omega fatty acids on the short-term postprandial satiety related peptides in rats

We aimed to assess the effects of omega fatty acids on time depending on responses of satiety hormones. Sixty adult rats were randomly divided into 4 groups; linoleic acid (LA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) groups. For each fatty acid, the dose of 400 mg/kg was applied by oral gavage. Blood samples were taken after the 15, 30, 60 and 120 minutes. Ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin and insulin hormones were analyzed by ELISA. We observed the significant increases (p<0.05) of the levels of CCK between n-3 (ALA, at 60th min; EPA, at 30th and 60th min and DHA, at 60 min) and n-6 (LA) supplemented rats. The highest GLP-1 levels were in ALA (0.70 ng/mL) and DHA (0.67 ng/mL) supplemented groups at 60th and 120th min indicating n-3 fatty acids efficiency on satiety compared to LA. It seems that ALA at 60th min and EPA at 120th min could provide the highest satiety effect with the highest insulin response, while the efficiency of LA supplementation on insulin-induced satiety diminished. The only significant change in AUC values among all hormones was in the CCK of the ALA group (p=0.004). The level of leptin increased in DHA and EPA supplemented rats (p=0.140). Our results showed that dietary omega fatty acids influenced the releasing of hormones in different ways possibly depending on chain length or saturation degree. Comprehensive studies need to be addressed for each fatty acid on satiety-related peptide hormones.

Role of a Dual Glucose-Dependent Insulinotropic Peptide (GIP)/Glucagon-like Peptide-1 Receptor Agonist (Twincretin) in Glycemic Control: From Pathophysiology to Treatment

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are two gut hormones, defined incretins, responsible for the amplification of insulin secretion after oral glucose intake. Unlike GLP-1, GIP has little acute effect on insulin secretion and no effect on food intake; instead it seems that the GIP may be an obesity-promoting hormone. In patients with type2 diabetes mellitus (T2DM) some studies found a downregulation of GIP receptors on pancreatic β cells caused by hyperglycemic state, but the glucagonotropic effect persisted. Agonists of the receptor for the GLP-1 have proven successful for the treatment of diabetes, since they reduce the risk for cardiovascular and renal events, but the possible application of GIP as therapy for T2DM is discussed. Moreover, the latest evidence showed a synergetic effect when GIP was combined with GLP-1 in monomolecular co-agonists. In fact, compared with the separate infusion of each hormone, the combination increased both insulin response and glucagonostatic response. In accordance with theseconsiderations, a dual GIP/GLP-1receptor agonist, i.e., Tirzepatide, known as a “twincretin” had been developed. In the pre-clinical trials, as well as Phase 1–3 clinical trials, Tirzepatideshowedpotent glucose lowering and weight loss effects within an acceptable safety.

Comprehensive transcriptional profiling and mouse phenotyping reveals dispensable role for adipose tissue selective long noncoding RNA Gm15551

Cold and nutrient activated brown adipose tissue (BAT) is capable of increasing systemic energy expenditure via uncoupled respiration and secretion of endocrine factors thereby protecting mice against diet-induced obesity and improving insulin response and glucose tolerance in men. Long non-coding RNAs (lncRNAs) have recently been identified as fine tuning regulators of cellular function. While certain lncRNAs have been functionally characterised in adipose tissue, their overall contribution in the activation of BAT remains elusive. We identified lncRNAs correlating to interscapular brown adipose tissue (iBAT) function in high fat diet (HFD) and cold stressed mice. We focused on Gm15551 which has an adipose tissue specific expression profile, is highly upregulated during adipogenesis and downregulated by β-adrenergic activation in mature adipocytes. Albeit we performed comprehensive transcriptional and adipocyte physiology profiling in vitro and in vivo, we could not detect an effect of gain or loss of function of Gm15551.

METHODS OF SCREENING TESTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS COMPLICATED BY PARTIAL ABSENCE OF TEETH

Рост числа больных сахарным диабетом 2 типа в мире носит характер эпидемии. Сахарный диабет 2-го типа - это нарушение углеводного обмена, который характеризуется комбинацией резистентности к инсулину и неадекватной реакции инсулина. Степень гипергликемии при этом типе сахарного диабета достаточна, чтобы привести к функциональным и патологическим изменениям в органах-мишенях, но эта гипергликемия еще не вызывает клинических симптомов и может существовать в течение длительного периода времени до момента выявления диабета. Заболевание до определенного момента носит скрытый характер, что обусловливает позднее выявление и, соответственно, несвоевременное лечение. Это приводит к высокой частоте сосудистых осложнений, ранней инвалидизации и смертности больных. Однако, в течение этого периода, можно путём определения глюкозы плазмы натощак и после пероральной нагрузки глюкозой обнаружить нарушение углеводного обмена. Изучение гликемической изменчивости - является важным компонентом системного подхода к контролю качества и компенсации сахарного диабета. Показатели гликемии натощак и гликемии через два часа после нагрузки проводили с целью подтверждения диагноза - сахарный диабет. Уровень гликированного гемоглобина HbAIc считается золотым стандартом в оценке гликемического статуса пациентов с сахарным диабетом. Гликемический контроль - это метод диагностики сахарного диабета 2-го типа снижения риска развития осложнений диабета, с целью предотвращения, задержки, замедления или остановки развития поздних осложнений. Было доказано, что гликированный гемоглобин оказался достоверен, продемонстрировав корреляцию со средними гликемическими значениями, а также отразил среднюю концентрацию глюкозы в крови за предыдущие два-три месяца. В этой связи становится актуальным повышение качества проводимых скрининговых обследований населения по выявлению нарушений углеводного обмена. Использование теста на определение гликированного гемоглобина HbA1c представляется наиболее информативным и экономически обоснованным. Вместе с этим ключевое значение приобретает выбор способа измерения гликогемоглобина (HbA1c). Он должен быть стандартизован по референсной методике - высокоэффективной жидкостной хроматографии, в соответствии с результатами исследований DCCT и UKPDS The increase in the number of patients with type 2 diabetes in the world has the character of an epidemic. Type 2 diabetes mellitus is a violation of carbohydrate metabolism, which is characterized by a combination of insulin resistance and an inadequate insulin response. The degree of hyperglycemia in this type of diabetes mellitus is sufficient to lead to functional and pathological changes in target organs, but this hyperglycemia does not yet cause clinical symptoms and can exist for a long period of time until diabetes is detected. The disease is latent up to a certain point, which causes late detection and, accordingly, untimely treatment. This leads to a high frequency of vascular complications, early disability and mortality of patients. However, during this period, it is possible to detect a violation of carbohydrate metabolism by determining fasting plasma glucose and after oral glucose loading. The study of glycemic variability is an important component of a systematic approach to quality control and compensation of diabetes mellitus. Indicators of fasting glycemia and glycemia two hours after exercise were carried out to confirm the diagnosis - diabetes mellitus. The level of glycated hemoglobin HbAic is considered the gold standard in assessing the glycemic status of patients with diabetes mellitus. Glycemic control is a method of diagnosing type 2 diabetes mellitus, reducing the risk of developing complications of diabetes, in order to prevent, delay, slow down or stop the development of late complications. It was proved that glycated hemoglobin was reliable, demonstrating a correlation with average glycemic values, and also reflected the average concentration of glucose in the blood over the previous two to three months. In this regard, it becomes urgent to improve the quality of screening surveys of the population to identify disorders of carbohydrate metabolism. The use of a test for the determination of glycated hemoglobin HbA1c seems to be the most informative and economically justified. At the same time, the choice of the method of measuring glycohemoglobin (HbA1c) becomes of key importance. It should be standardized according to the reference method - high-performance liquid chromatography, in accordance with the results of DCCT and UKPDS studies

Diets with Higher Insulinemic Potential Are Associated with Increased Risk of Overall and Cardiovascular Disease-specific Mortality

Hyperinsulinemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-hour recalls. Two empirical dietary indices for hyperinsulinemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinemia (C-peptide and insulin) and insulin resistance (homeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until December 31, 2015 were identified by the National Death Index. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models. During a median follow-up of 7.8 years, 4,904 deaths were documented among 40,074 participants. For EDIH, the multivariable-adjusted HRs (comparing extreme quintiles) were 1.20 (95% CI: 1.09-1.32, P-trend<0.001) for overall mortality, and 1.41 (95% CI: 1.15-1.74, P-trend=0.002) for cardiovascular disease (CVD) mortality. Similar associations were observed for EDIR with HRs of 1.18 (95% CI: 1.07-1.29, P-trend<0.001) for total and 1.35 (95% CI: 1.09-1.67, P-trend=0.005) for CVD mortality. After further adjustments for body mass index and diabetes, these positive associations were somewhat attenuated, but most remained statistically significant. Our findings suggested that diets with higher insulinemic potential are associated with increased risk of overall and CVD-specific mortality. Strategies to avoid hyperinsulinemic dietary patterns may potentially promote health and longevity.

The role of r esistant starch in human nutrition

In this paper, we examine the role and effect of resistant starch (RS) in human nutrition; further, the structure and properties of RS, the food sources based on resistance to digestion in the colon, and the physiological effects of RS are described. The nutritional value of RS, the effect of RS on short-chain fatty acid (SCFA) production, the relationships between RS and colon function, and the relationships between food starch, dietary fibre, and RS content and colon cancer development are reviewed. It has been shown that the use of RS in foods may have some benefits. Resistant starch, digestion of resistant-starch-containing foods have a number of health benefits for colon function but appear to have less effect on lipid-glucose metabolism. It has a positive effect on colon bacterial activity, promotes the growth of beneficial microbes, and reduces the activity of enzymes that are harmful to the digestive system. Under the influence of RS, increased SCFA production lowers the pH of the colon and stimulates bile acid secretion. The decreased pH protects against colon cancer and inhibits the conversion of primary and secondary bile acids, which are cytotoxic to intestinal cells. At the end of the review article, the relationships between RS and the colon microflora, its use as a prebiotic, and the relationship between RS and glucose metabolism are analysed. It was found that the use of RS in the diet might have benefits as it shortens the time it takes food to pass through the colon and increases the amount of stool. It was also found that the physicochemical properties of foods can directly affect the amount of RS and thereby the blood glucose levels and insulin response.