Increased Insulin Resistance Research Articles

A Rare association of Mauriac syndrome and Van-Wyk Grumbach syndrome found in a young Saudi girl with poorly controlled type 1 Diabetes and Hypothyroidism: A Case Report and Brief literature review

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insufficient insulin production of the pancreatic beta-cells. Patients with T1DM will have a higher risk of other autoimmune disorders like celiac and thyroid diseases. Hypothyroidism is the failure of the thyroid gland to secrete an adequate amount of thyroxine, which is required for physical growth, brain development, and cellular metabolism. Most studies reported that children with T1DM have a higher incidence of hypothyroidism than normal children, with 9.6% having hypothyroidism and 19% having positive anti-TPO antibodies. Hypothyroidism will aggravate the condition in a child with T1DM and vice versa. Uncontrolled diabetes for a long time might increase insulin resistance due to complete depression of the hypothalamus-pituitary thyroid axis. A rare complication of poorly controlled T1DM is Mauriac syndrome, characterized by elevated liver enzymes, hyperlipidemia, cushingoid features, growth retardation, and hepatomegaly due to glycogenic hepatopathy. Van Wyk–Grumbach syndrome is also a rare complication of long-standing, untreated hypothyroidism, manifested by breast development, multicystic ovary, uterine bleeding associated with lack of pubic and axillary hair growth, and delayed bone age. Here, we report a case with two rare complications of Mauriac syndrome and Van Wyk–Grumbach syndrome in a child with hypothyroidism and poorly controlled T1DM.

Should Carbohydrate Intake Be More Liberal during Oral and Enteral Nutrition in Type 2 Diabetic Patients?

Carbohydrate (CHO) intake in oral and enteral nutrition is regularly reduced in nutritional support of older patients due to the high prevalence of diabetes (usually type 2-T2DM) in this age group. However, CHO shortage can lead to the lack of building blocks necessary for tissue regeneration and other anabolic processes. Moreover, low CHO intake decreases CHO oxidation and can increase insulin resistance. The aim of our current study was to determine the extent to which an increased intake of a rapidly digestible carbohydrate-maltodextrin-affects blood glucose levels monitored continuously for one week in patients with and without T2DM. Twenty-one patients (14 T2DM and seven without diabetes) were studied for two weeks. During the first week, patients with T2DM received standard diabetic nutrition (250 g CHO per day) and patients without diabetes received a standard diet (350 g of CHO per day). During the second week, the daily CHO intake was increased to 400 in T2DM and 500 g in nondiabetic patients by addition of 150 g maltodextrin divided into three equal doses of 50 g and given immediately after the main meal. Plasma glucose level was monitored continually with the help of a subcutaneous sensor during both weeks. The increased CHO intake led to transient postprandial increase of glucose levels in T2DM patients. This rise was more manifest during the first three days of CHO intake, and then the postprandial peak hyperglycemia was blunted. During the night's fasting period, the glucose levels were not influenced by maltodextrin. Supplementation of additional CHO did not influence the percentual range of high glucose level and decreased a risk of hypoglycaemia. No change in T2DM treatment was indicated. The results confirm our assumption that increased CHO intake as an alternative to CHO restriction in type 2 diabetic patients during oral and enteral nutritional support is safe.

Hepatocyte PPARγ contributes to the progression of non-alcoholic steatohepatitis in male and female obese mice.

Non-alcoholic steatohepatitis (NASH) is associated with obesity and increased expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ). However, the relevance of hepatocyte PPARγ in NASH associated with obesity is still poorly understood. In this study, hepatocyte PPARγ was knocked out (PpargΔHep) in male and female mice after the development of high-fat diet-induced obesity. The diet-induced obese mice were then maintained on their original diet or switched to a high fat, cholesterol, and fructose (HFCF) diet to induce NASH. Hepatic PPARγ expression was mostly derived from hepatocytes and increased by high fat diets. PpargΔHep reduced HFCF-induced NASH progression without altering steatosis, reduced the expression of key genes involved in hepatic fibrosis in HFCF-fed male and female mice, and decreased the area of collagen-stained fibrosis in the liver of HFCF-fed male mice. Moreover, transcriptomic and metabolomic data suggested that HFCF-diet regulated hepatic amino acid metabolism in a hepatocyte PPARγ-dependent manner. PpargΔHep increased betaine-homocysteine s-methyltransferase expression and reduced homocysteine levels in HFCF-fed male mice. In addition, in a cohort of 102 obese patients undergoing bariatric surgery with liver biopsies, 16 cases were scored with NASH and were associated with increased insulin resistance and hepatic PPARγexpression. Our study shows that hepatocyte PPARγ expression is associated with NASH in mice and humans. In male mice, hepatocyte PPARγ negatively regulates methionine metabolism and contributes to the progression of fibrosis.

Extracellular vesicles regulate the transmission of insulin resistance and redefine noncommunicable diseases.

Noncommunicable diseases (NCDs), such as diabetes and related neurological disorders, are considered to not be directly transmissible from one person to another. However, NCDs may be transmissible in vivo through extracellular vesicles (EVs). A long-term high-fat diet (HFD) can induce a series of health issues like hyperlipidemia, type 2 diabetes mellitus (T2DM), and diabetic peripheral neuropathy (DPN) due to insulin resistance. Multiple molecular signaling changes can stimulate insulin resistance, especially blocking insulin signaling by increased insulin resistance inducer (phosphorylation of negative regulatory sites of insulin receptor substrate (IRS) proteins) and decreased tyrosine phosphorylation of insulin receptor substrate (phosphorylation of positive regulatory sites of IRS), thus leading to reduced phosphorylation of AKT enzymes. Current efforts to treat T2DM and prevent its complications mainly focus on improving insulin sensitivity, enhancing insulin secretion, or supplementing exogenous insulin based on a common assumption that insulin resistance is noncommunicable. However, insulin resistance is transmissible within multiple tissues or organs throughout the body. Exploring the regulatory roles of EVs in developing insulin resistance may provide novel and effective preventive and therapeutic strategies.

Modulation of Burn Hypermetabolism in Preclinical Models.

Severe burns elicit a state of physiological stress and increased metabolism to help the body compensate for the changes associated with the traumatic injury. However, this hypermetabolic state is associated with increased insulin resistance, cardiovascular dysfunction, skeletal muscle catabolism, impaired wound healing, and delayed recovery. Several interventions were attempted to modulate burn hypermetabolism, including nutritional support, early excision and grafting, and growth hormone application. However, burn hypermetabolism still imposes significant morbidity and mortality in burn patients. Due to the limitations of in vitro models, animal models are indispensable in burn research. Animal models provide researchers with invaluable tools to test the safety and efficacy of novel treatments or advance our knowledge of previously utilized agents. Several animal studies evaluated novel therapies to modulate burn hypermetabolism in the last few years, including recombinant human growth hormone, erythropoietin, acipimox, apelin, anti-interleukin-6 monoclonal antibody, and ghrelin therapies. Results from these studies are promising and may be effectively translated into human studies. In addition, other studies revisited drugs previously used in clinical practice, such as insulin and metformin, to further investigate their underlying mechanisms as modulators of burn hypermetabolism. This review aims to update burn experts with the novel therapies under investigation in burn hypermetabolism with a focus on applicability and translation. Furthermore, we aim to guide researchers in selecting the correct animal model for their experiments by providing a summary of the methodology and the rationale of the latest studies.

The Relationship between Diabetes Mellitus and Pancreatic Cancer-Diabetes Mellitus as a Red Flag for Pancreatic Cancer.

The relationship between diabetes mellitus (DM) and pancreatic cancer is complex-DM is both a risk factor and early sign of pancreatic cancer. DM is a risk factor for pancreatic cancer because it increases insulin resistance, intrapancreatic concentrations of insulin, and the bioavailability of IGF, subsequently promoting ductal cell proliferation. Accordingly, treatment targeting the insulin/IGF pathway is the focus of many researchers. Antidiabetic drugs modify the risk for pancreatic cancer-metformin's antineoplastic effect being most notable and indicating potential clinical use in pancreatic cancer. New-onset DM can also be the first manifestation of pancreatic cancer. There are several theories for the pathogenesis of DM in pancreatic cancer, the most important being that DM is a paraneoplastic syndrome caused by diabetogenic factors. As a consequence of this intricate relationship, new-onset DM after the age of 50 is considered a red flag for pancreatic cancer, prompting the need for screening in this patient population. Multiple clinical studies are currently underway exploring this matter. A better understanding of the relationship between DM and pancreatic cancer could aid in developing novel screening and treatment strategies for pancreatic cancer. This could ultimately improve the prognosis and quality of life of patients with pancreatic cancer.

Polycystic Ovaries: A Cross Sectional Study on Unmarried Girls in KSA

Polycystic ovaries often do not cause a disturbance in ovulation, and therefore it does not cause difficulties or problems in conceiving in most cases, but it also depends on the severity and size of the ovarian cysts. The causes of polycystic ovaries are not completely clear, but there are some factors that have a role in increasing the possibility of developing and developing this disorder, and these factors include obesity, family history, insulin resistance, inflammation in the body, which may increase insulin resistance. Polycystic ovary isn’t the same to Polycystic ovary syndrome. The predominant endocrine disease that is rapidly spreading to epidemic levels is PCOS. For this syndrome, there are no community- based prevalence data available in KSA. In order to determine the prevalence of Polycystic Ovary Syndrome (PCOS) among 778 girls and adolescents aged 15–24 years, a community cross-sectional study was conducted in a census block taken from Mumbai. Six hundred of them completed all clinical, ultrasound, and biochemical tests. According to the Rotterdam criteria and 10.7% according to the Androgen Excess Association criteria, they had a prevalence of PCOS of 22.5%. 71.8% of PCOS cases according to the Rotterdam criteria were not infected with H. pylori. The most prevalent phenotype (52.6%) was mild PCOS (oligomenorrhea and polycystic ovary syndrome on USG).

Pathologic subtypes in Japanese women with gestational diabetes

It has been suggested that two pathologic conditions, increased insulin resistance (IR) and impaired insulin secretion (IIS), are involved in the development of gestational diabetes mellitus (GDM). We attempted to classify women with GDM according to those pathologic subtypes and examine the association between the subtypes and perinatal and postpartum risk. We conducted a retrospective study of singleton women with GDM whose insulin were measured at a 75-g oral glucose tolerance test (OGTT) both during pregnancy and early postpartum. Homeostasis model assessment (HOMA) - IR and insulinogenic index (IGI) were used as indices of IR and insulin secretion, respectively. We defined IR as HOMA-IR ≥75%tile values of women with a normal OGTT result, and IIS as IGI < 0.4. The pathologic subtypes were classified into IR, IIS, mixed, and normal types. We examined the association between those subtypes and intensive insulin therapy (IIT) during pregnancy defined as requiring insulin ≥20 U/day and early postpartum abnormal glucose tolerance (AGT). 253 subjects were classified as follows: IR, 34%; IIS, 25%; mixed, 4%; normal, 37% during pregnancy. Compared with the normal subtype, women with the IR, IIS and mixed types were significantly associated with the IIT, while the incidence of postpartum AGT did not differ significantly (Table). 61% and 75% of women with the IR/mixed and IIS type during pregnancy persisted the same subtypes in the postpartum, respectively. Women with GDM with the pathologic subtypes were associated with the risk of insulin therapy. More than 60% of those women persisted the same abnormal subtypes in the early postpartum.

Increased insulin resistance due to Long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection.

Some months after the remission of acute COVID-19, some individuals show depressive symptoms, which are predicted by increased peak body temperature (PBT) and decreased blood oxygen saturation (SpO2). The present study aimed to examine data on whether long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes during the acute infectious and long COVID phases. This case-control, retrospective cohort study used the Homeostasis Model Assessment 2 (HOMA2) calculator© to compute ß-cell function (HOMA2%B) and insulin sensitivity (HOMA2%S) and resistance (HOMA2-IR) and administered the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) to 86 patients with long COVID and 39 controls. Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose (FBG), and insulin levels; 33.7% of the patients vs. 0% of the controls had HOMA2-IR values > 1.8, suggesting IR. Increased IR was predicted by PBT during acute infection and associated with depressive symptoms above and beyond the effects of NIO pathways (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3] inflammasome, myeloperoxidase [MPO], protein oxidation). There were no significant associations between increased IR and the activated NIO pathways during long COVID. Long COVID is associated with new-onset IR, which may contribute to onset of depressive symptoms due to long COVID by enhancing overall neurotoxicity.

Correlation of 25-Hydroxycholecalciferol and Glycaemic Status in Recent Onset Type 2 Diabetes Mellitus

Introduction: Type 2 Diabetes Mellitus (T2DM) is a non communicable disease caused by increased insulin resistance and beta cells dysfunction. Recently vitamin D has sparked wide spread interest in pathogenesis of diabetes by playing a role in insulin resistance. As a major regulator of homeostasis of calcium, vitamin D directly and/or indirectly improves insulin exocytosis and glucose tolerance. Aim: To estimate the serum 25 hydroxy cholecalciferol level and also to correlate with fasting, two hour postprandial blood glucose and Glycated Haemoglobin (HbA1c) values in recent onset T2DM patients. Materials and Methods: This cross-sectional study was conducted at Government Kilpauk Medical College, Tamil Nadu, India from November 2017-April 2018. One hundred and thirty nine recently diagnosed T2DM patients aged between 30-60 years of both sex, who were on oral hypoglycemic drugs for less than three months duration were included in the study. The patients were grouped into three groups according to their vitamin D levels, Group 1 Vitamin D deficient- 52 patients (≤20 ng/mL), Group 2- Insufficient Vitamin D -33 patients (&gt;20-30 ng/mL), Group 3- Vitamin D sufficient-54 patients (&gt;30 ng/mL). Fasting and 2 hour postprandial glucose, 25 hydroxy cholecalciferol and HbA1c were estimated. Statistical analysis was performed using analysis of variance (ANOVA) and Pearson’s correlation. Results: Out of 139 participants, 64 were males and 75 were females. The mean age of the study population was 50.64±5.343 years. The mean fasting blood glucose values among the three groups were 168.13, 129.61, and 125.33 mg/dL respectively. The mean two hour postprandial blood glucose values among the three groups were 269.44, 212.45, and 194.11 mg/dL respectively. The mean HbA1c among the three groups were 7.481±1.16, 6.027±0.31, and 5.86±0.19, respectively. Decreased 25 hydroxy cholecalciferol level in patients of T2DM showed a statistically significant inverse correlation with fasting and two hour postprandial blood glucose and HbA1c with p-value &lt;0.001. Conclusion: The study suggested that hypovitaminosis D was prevalent in T2DM. The study showed that decreased vitamin D level in T2DM patients was associated with increased fasting, postprandial blood sugar, and HbA1c. So, vitamin D screening in diabetics and supplementation can improve the glycemic status.

Kidney stones in patients with type 2 diabetes mellitus. Metabolic risk factors

Background: In the past few decades, the prevalence of kidney stones in Western countries has increased in parallel with the growing overweight/obesity and type 2 diabetes mellitus rates. An increased insulin resistance in these patients explains, in part, the rising prevalence of uric acid stones. Aim: The Aim of this retrospective study was to evaluate the metabolic abnormalities in type 2 diabetic and non-diabetic patients with kidney stones. Methods: A total of 104 diabetic patients (age: 57.8 ± 11 years) and 130 non-diabetics (age: 52.1 ± 6.7 years) with kidney stones were selected. Results: Higher rates of body mass index, hypertension, urinary tract infection, gout and hyperuricemia were observed in diabetic patients as compared to the non-diabetics, while similar rates were found for their family history of kidney stones. Metabolic abnormalities were detected in 95.2% and 81.5% of diabetics and non-diabetics, respectively. Idiopathic hypercalciuria was the most frequent abnormality in both groups, although as a simple abnormality, in diabetic patients, unduly acidic urine was the more common. Conclusions: unduly acidic urine is the most frequent single abnormalities in patients with diabetes mellitus and is in part responsible for the greater number of uric acid stones.

Особенности метаболизма у женщин с преэклампсией, сочетающейся с гестационным сахарным диабетом

Objective of the Review: To summarize the proven prognostic and diagnostic criteria for gestational complications caused by a combination of gestational diabetes mellitus (GDM) and preeclampsia (PE). Key points. There is an analytical review of the modern paradigm of GDM and PE, their complications, as well as perinatal and long-term outcomes for mother and child. The data on clinical, anamnestic and laboratory risk factors of PE in GDM are systematized. A close relationship between the mechanisms of PE and GDM development — angiogenic imbalance and metabolic disorders in the placenta is described. Conclusion. GDM is recognized as an independent risk factor for the development of PE, and this risk is the greater the less GDM is compensated. Polycystic ovary syndrome and an increased body mass index as concomitant factors of metabolic disorders also increase the risk of developing PE. The supposed pathogenetic commonality of GDM and PE is the presence of oxidative stress and metaflammation, which increase insulin resistance and cause endothelial dysfunction. Keywords: preeclampsia, gestational diabetes mellitus, metabolism, risk factors, pathogenetic commonality.

Higher Levels of Plasma Fetuin-A, Nrf2, and Cytokeratin 18 in Patients with Hashimoto's Disease.

Fetuin-A is a protein that exhibits proatherogenic, pro-inflammatory, and anti-inflammatory effects with increased insulin resistance and adipocyte dysfunction. The nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that is crucial for protecting cells against oxidative damage. As a cell death product, cytokeratin 18 (CK18) levels increase during necrosis and apoptosis of both normal and tumor cells. We analyzed the plasma levels of three biomarkers based on the hypothesis that they might be related to some pathophysiological pathways in Hashimoto's disease. We compared 34 female patients with overt hypothyroidism due to Hashimoto's disease (Group 1) with 34 age-matched healthy females (Group 2). For comparison, plasma levels of thyroid-stimulating hormone (TSH), fetuin-A, Nrf2, and CK18 were measured in all participants. In group 1, the mean TSH levels (31.4±15.3) were significantly higher than those in group 2 (2.6±1.0) (p<0.001). The levels of mean fetuin-A (606.7±34.2) and Nrf2 (1.3±0.6) were found to be significantly higher in group 1 than in group 2 (440.0±34.2 vs. 0.7±0.2) (p<0.001 for both). CK18 levels in group 1 (0.36±0.13) were also significantly higher than in group 2 (0.26±0.16) (p=0.020). A significant correlation was observed between TSH levels and fetuin-A (r=0.401, p=0.001). Increased levels of fetuin-A, Nrf2, and CK18 may be a consequence or cause of the pathophysiological pathways of Hashimoto's disease. The clinical significance of increased levels of these biomarkers requires further investigation.

S-44-6: ASSESSING THE EFFECT OF SIMPLE CARBOHYDRATE RESTRICTED DIET ON BLOOD PRESSURE LEVELS OF HYPERTENSIVE

Objective: In the recent past, various functional foods have been proposed to be effective tools for alleviating hypertension. There is a paucity of evidence on the efficacy of restricted sugar intake in an Indian setting and most evidence comes from non-validated studies. Studies have proposed that sugar acts by decreasing nitric oxide, increasing low-grade inflammation, increasing insulin resistance and promoting obesity. The objective of the study is to assess the efficacy of restriction of simple carbohydrate intake on change in body weight, blood pressure and anthropometry [waist circumference (WC), waist to hip ratio(WHR) and body mass index (BMI)] after 30 days in males with pre-dominant hypertension. Design and Methods: A Case-Control Study with a sample size of 200 urban patients with clinical blood pressure &gt; 140/90 were selected and divided into 2 groups. A 1800kcal/day diet restricted in simple carbohydrates was given and Blood pressure, body weight, anthropometry (height, WC, HC, BMI, WHR, BSL (F, PP) were measured after 30 days. The participants had been following a structured 1800 kcal/day 3 months prior to the carbohydrate-restricted intervention. Complex carbohydrates were allowed. No change in physical activity was initiated. Results: A significant reduction was observed in the intervention group consuming a restricted carbohydrate diet along with a structured diet. Diet recall was taken using food frequency questionnaires and daily pictures of the plate that the participants consumed. Conclusion: A restricted simple carbohydrate diet was found to be effective in weight loss and reduction of systolic and diastolic blood pressure in patients with hypertension. The intervention group has a higher odds ratio and is positively associated with SBP, Weight loss and WC as compared to the control group. The source of simple carbohydrates in the majority of the participants was noted as bakery products, sauces and other hidden sources of carbohydrates. Participants were regularly counselled towards healthy eating and dietary sources of various nutrients.

Consumption of Junk Foods and Risk of Type 2 Diabetes: A Review

According to the estimation of International Diabetes Federation (IDF) 2021, there are 537 million diabetics worldwide. The purpose of the current review is to explore the relationship between consumption of junk food and type 2 diabetes. Junk food is defined as being easily accessible, typically inexpensive, and having low nutritive value. These foods have lesser amounts of iron, calcium, and dietary fiber and are higher in calories, salt, and saturated fat. Unhealthy diet is one of the important lifestyle factors responsible for several health conditions. Junk foods includes deep fried, processed or ultra-processed foods (UPFs) and high sugar containing foodstuffs and beverages such as Sugar Sweetened Beverages (SSBs) are directly linked with higher body mass index (BMI), adiposity and increased insulin resistance (IR). For pertinent databases IDF Atlas reports, PubMed, Springer, Elsevier, Web of Science and BMJ were searched for original and meta-analysis studies published up to March, 2023. In recent decades, consumption of these foods has significantly increased worldwide. The primary risk factor for type 2 diabetes is obesity and consuming junk foods is strongly associated with being obese. Junk food consequences include an increase in type 2 diabetes cases especially among youths and adult women compared to men. Obesity or high BMI indicate a positive energy balance due to junk food intake. As a result, the recurrent consumption of junk food increases the likelihood of developing the type 2 diabetes.

Update on the Role of Adequate Vitamin D Provision for Avoiding Insulin Resistance and its Sequelae [Type 2 Diabetes and Cardiovascular Disease

Type 2 diabetes prevalence is increasing, reaching ‘pandemic’ proportions globally, and associated with increasing obesity rates. Concomitantly, vitamin D deficiency persists world-wide and is worsened by obesity because it reduces hepatic 25-hydroxylation of vitamin D, which reduces circulating 25(OH)D availability to target tissues; these include islet beta cells, since vitamin D is essential for adequate insulin responses to hyperglycemia. Increased insulin resistance increases type-2 diabetes risks and precedes its development by decades, reflecting changes in hepatic and muscle function that are corrected experimentally by activated hormonal vitamin D [calcitriol]; similarly, abnormal insulin resistance can be corrected in humans by correcting vitamin D deficiency using oral supplementation. Since vitamin D deficiency and inadequacy persist world-wide despite various guidelines on vitamin D intake, the possibility that correcting deficiency would contribute to reducing T2DM risks through beneficial effects on pancreatic islet beta cells and on the metabolic disorders contributing to insulin resistance through vitamin D inadequacy warrants consideration. If this is the case, then ensuring vitamin D adequacy in populations at high risk of Type-2 diabetes would be a valuable adjunct to other measures being taken to reduce that risk such as increased exercise and weight reduction. It would also reduce cardiovascular disease risks, well known to increase with insulin resistance, with or without concomitant Type-2 diabetes. Cardiovascular disease risks themselves can be reduced by adequately correcting deficiency and are lower with higher lifetime circulating 25-hydroxyvitamin D in deficient subjects from Mendelian randomization analysis. This report, therefore, reviews the evidence for increased insulin resistance as a risk factor for Type-2 diabetes, the beneficial effects of correcting vitamin deficiency on insulin resistance, Type-2 diabetes and cardiovascular risks, some basic mechanisms accounting for those benefits, the reasons for the persistence of vitamin D inadequacy globally and how best that problem could be corrected.

Dose-dependent effects of xylooligosaccharides on glycemic regulation with L. rhamnosus CCFM1060 in diabetic mice.

Dietary intervention with the probiotic Lactobacillus rhamnosus CCFM1060 has been proved to be effective on glycemic regulation in diabetic mice. Therefore characterization of the potential symbiotic effect of prebiotic xylooligosaccharides (XOS) with L. rhamnosus CCFM1060 would be desirable. In this study, we evaluated any dose-dependent relationship between XOS and L. rhamnosus CCFM1060, and the potential impact on glycemic regulation. Diabetic mice were randomly assigned to receive 5 × 109 CFU mL-1L. rhamnosus CCFM1060, 5 × 109 CFU mL-1L. rhamnosus CCFM1060 with 250 mg kg-1 XOS (L-LXOS), or 5 × 109 CFU mL-1L. rhamnosus CCFM1060 with 500 mg kg-1 XOS (L-HXOS) for 7 weeks. In addition to characterization of the host metabolism, the intestinal microbiota were analyzed using 16S rRNA gene sequencing. The results showed that L. rhamnosus alone and L-LXOS intervention significantly alleviated diabetes symptoms and increased the populations of short-chain fatty acid (SCFA)-producing bacteria. The intake of L-HXOS had an adverse effect on glucose metabolism, causing increased insulin resistance and inflammation. Although a significant increase in the relative abundance of Bifidobacterium was observed in the L-HXOS group, the abundance of SCFA-producing bacteria, such as Romboutsia and Clostrudium sensu stricto 1, decreased. KEGG pathway analysis revealed that the adverse effects of L-HXOS intervention might be attributed to the metabolic pathways involved in amino acid, cofactor, and vitamin metabolism. This study revealed that L. rhamnosus CCFM1060 combined with different doses of XOS exerted dose-dependent effects on glucose metabolism. Therefore, the type and dose of prebiotics should be carefully evaluated when developing individualized symbiotic formula.

The Relationship between Serum Ferritin Level and Insulin Resistance in Metabolic Syndrome

Introduction: Insulin resistance and metabolic syndrome (MetS) are risk factors for diabetes mellitus, and their prevalence is increasing. Ferritin has emerged as a biomarker of low-grade inflammation in addition to its role in iron metabolism. The study aims to determine the correlation between ferritin and insulin resistance (IR) in MetS. Materials and Methods: In this study, ferritin, glucose (fasting), and HOMA-IR were measured from serum samples obtained from 98 MetS patients and 100 healthy volunteers. Serum ferritin, glucose, insulin, and HOMA-IR results were compared between the MetS and the control group. Correlation analysis was performed between ferritin and HOMA-IR in control and MetS patients. Results: Serum ferritin (Control: 93,9±30,13; MetS:200±57,31 ng/ml), glucose (Control: 100,9±11,86, 123,9±21,52 ng/dl), insulin (Control: 4,11±2,57; MetS:15,99±5,71 µU/ml) and HOMA-IR (Control: 1,04±0,74; MetS:5,07±2,33) revealed to be higher in MetS compared to control. The correlation between serum ferritin level and HOMA-IR in MetS patients was revealed. This correlation was not found in the control group. Conclusion: In MetS, high serum ferritin level increases insulin resistance. While the positive correlation of ferritin with insulin resistance occurs at high ferritin levels, this is not observed at low ferritin levels.

Pluchea indica Leaf Extract Alleviates Dyslipidemia and Hepatic Steatosis by Modifying the Expression of Lipid Metabolism-Related Genes in Rats Fed a High Fat-High Fructose Diet.

This study evaluated the effect of Pluchea indica leaf extract (PIE) on dyslipidemia and lipid accumulation in the liver, emphasizing its molecular mechanisms in regulating lipid metabolism in rats fed a high fat-high fructose diet (HFFD). Male rats were fed HFFD (40% lard and 20% fructose) for ten weeks. They were then divided into four groups receiving distilled water, PIE (100 or 300 mg/kg/d), and pioglitazone (10 mg/kg/d) for a further six weeks, during which the HFFD was continued. After the experiment, fasting blood glucose (FBG), oral glucose tolerance (OGT), serum insulin and leptin levels, lipid profiles, and hepatic triglyceride content were measured. Histological examination and expression levels of lipid metabolism-related genes in the liver were measured. HFFD-fed rats indicated a significantly increased FBG, serum leptin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores with impaired OGT and dyslipidemia compared to rats fed a normal diet. PIE significantly reduced FBG, serum leptin, and HOMA-IR scores and improved OGT. Additionally, PIE significantly improved dyslipidemia and decreased serum-free fatty acids and liver triglyceride content. Hepatic histological examination showed a marked reduction lipid accumulation in relation to HFFD controls. Interestingly, PIE significantly downregulated the expression of lipid synthesis-related genes and upregulated the expression of fatty-acid oxidation-related genes. In conclusion, PIE alleviates dyslipidemia and hepatic steatosis in HFFD rats plausibly by increasing insulin resistance and modifying the gene expression associated with lipid metabolism. PIE may be used as preventive nutrition for dyslipidemia and hepatic steatosis.

Diabetogenic liver metastasis from pancreatic cancer: a case report

BackgroundAlthough new-onset diabetes has been described in up to 20% of patients with newly diagnosed pancreatic cancer, reports regarding new-onset diabetes associated with newly developed liver metastasis from pancreatic cancer are limited.Case presentationA 60-year-old man was diagnosed with pancreatic tail cancer without impaired glycemic control. A curative-intent distal pancreatectomy with adjuvant S-1 chemotherapy was performed. Two years after surgery, a high HbA1c concentration and solitary liver metastasis were identified on follow-up examination. Two major chemotherapy regimens, gemcitabine/nab-paclitaxel and modified FOLFIRINOX, were sequentially administered to the patient; however, his carbohydrate 19-9 concentration continued to increase. Because the patient’s glycemic control rapidly worsened in synchrony with the tumor growth, insulin therapy was initiated. Although the liver metastasis was refractory to chemotherapy, curative-intent left hepatectomy was performed because only one tumor remained. His impaired glycemic control improved immediately after surgery, and insulin therapy was terminated. When writing this report (2 years after hepatectomy), the patient was alive and recurrence-free.ConclusionsNew-onset diabetes appeared with the progression of metachronous liver metastasis from pancreatic cancer, without recurrence at any other site. The patient’s diabetic state was improved by resection of the liver tumor, and liver metastasis itself was proven to have caused the glucometabolic disorder by increasing insulin resistance.