Diabetes Insulin Resistance Research Articles

Therapeutic potential of SGLT-2 inhibitors and DDP4 inhibitors in elderly patients with type 2 diabetes mellitus and benign prostatic hyperplasia

Background. Benign prostatic hyperplasia (BPH) has recently been linked to diabetes mellitus and insulin resistance. This study aims to explore whether the use of either sodium-glucose co-transporter-2 (SGLT-2) inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with favorable outcomes in prostate volume and symptoms. Methods. This is a before-and-after study involving 57 elderly male patients with type 2 diabetes mellitus and BPH, who were recruited and followed up for one year. Twenty-seven patients were prescribed SGLT-2 inhibitors (Dapagliflozin 10 mg), and thirty patients were prescribed DPP-4 inhibitors (Sitagliptin 100 mg). Prostate volume, International Prostate Symptom Score (IPSS), and Pittsburgh Sleep Quality Index (PSQI) were assessed in all patients. Results. The use of either SGLT-2 inhibitors or DPP-4 inhibitors was associated with a statistically significant decrease in prostate volume after one year of treatment (p = 0.04 for SGLT-2 inhibitors and p = 0.02 for DPP-4 inhibitors). Statistically significant reductions were found in both groups regarding post-voiding urine volume after one year of treatment compared to baseline levels (p = 0.014 for SGLT-2 inhibitors and p = 0.017 for DPP-4 inhibitors). At the end of the follow-up period, there was a statistically significant reduction in IPSS scores (p = 0.02 for SGLT-2 inhibitors and p = 0.03 for DPP-4 inhibitors). Similarly, the use of either DPP-4 inhibitors or SGLT-2 inhibitors was associated with a statistically significant improvement in nocturia and sleep quality (PSQI score) (p = 0.012 for SGLT-2 inhibitors and p = 0.01 for DPP-4 inhibitors). Post-hoc analysis showed that DPP-4 inhibitors were superior to SGLT-2 inhibitors in reducing prostate volume and symptoms (p < 0.05). Conclusion. Both SGLT-2 inhibitors and DPP-4 inhibitors improve prostate volume and symptoms in patients with diabetes mellitus and BPH. Notably, DPP-4 inhibitors exhibited superiority over SGLT-2 inhibitors in terms of reducing prostate volume and alleviating symptoms. Larger-scale studies are required to confirm these favorable effects.

An overview on pharmaceutical applications of phosphodiesterase enzyme 5 (PDE5) inhibitors.

Phosphodiesterase enzyme 5 (PDE5) inhibitors have emerged as one of the leading molecules for the treatment of erectile dysfunction (ED). PDE5 inhibitors are categorized structurally into several classes. PDE5 inhibitors have been a multidisciplinary endeavor that attracts the attention of researchers because of their multiple pharmaceutical applications. Beyond their action on ED, PDE5 inhibitors are widely used in treatment of benign prostatic hypertrophy (BPH), Eisenmenger's syndrome, Raynaud's Disease, Intrauterine growth retardation (IUGR), Mountain sickness, Bladder pain syndrome/interstitial cystitis (BPS/IC), pulmonary arterial hypertension and type II diabetes (insulin resistance). In addition, PDE5 inhibitors also show promising antiproliferative activity, anti-Alzheimer and COX-1/COX-2 inhibitory activity (anti-inflammatory). Pharmacokinetics, Pharmacogenetics and toxicity of PDE5 inhibitors were finally explored. The diverse therapeutic applications, the high feasibility of structural modification and the appropriate pharmacokinetic properties of PDE5 inhibitors have motivated researchers to develop new scaffolds that have been either under clinical trials or approved by FDA and utilize them to overcome some recent global concerns, such as COVID-19.

Investigating the potential role of T helper 17 cells among women experiencing overweight and obesity and their possible therapeutic targeting of the RORγt molecule

Obesity is a growing healthcare problem globally. In Saudi Arabia, 24% of adults aged 15 years and above have been living with Obesity. It is considered a chronic inflammatory condition that is linked to a wide range of disorders including type 2 diabetes mellitus, insulin resistance and cardiovascular diseases. In this study, we aimed to assess the influence of obesity on the proportion of Th17 cells among healthy, overweight, and obese women in Saudi Arabia. Additionally, we aimed to explore potential ligands targeting the master transcription factor of Th17 cells: RORγt. A cross-sectional study was conducted, wherein their body mass index (BMI) and waist circumference (WC) were measured. The proportion of peripheral Th17 cells was determined using flow cytometry. We found a decrease in the proportion of peripheral Th17 among women with central obesity, though this was observed among overweight and obese participants. Interestingly, both BMI and WC were inversely correlated with the proportion of peripheral Th17 cells in women experiencing overweight or obesity, while no change was observed among healthy participants. Notably, the analysis revealed a significant moderate negative correlation between the proportion of Th17 cells and HbA1c levels, observed only among the overweight and obese participants. In this study, we identified three potential binding sites on RORγt molecules of Th17 cells, bound to 58 chemical ligands. The majority of the chemical structures (72.4%) were targeted binding pocket 1 of the RORγt molecule. These findings could provide a new insight to develop new pharmaceutical molecules targeting immune cells to combat obesity and related metabolic disorders.

Examining symptom and quality of life in polycystic ovarian syndrome: a web-based cross-sectional study.

Polycystic Ovarian Syndrome (PCOS) is a reproductive disorder that significantly impacts women's quality of life (QOL). Its unclear etiology, whether genetic or environmental, and the treatments associated with it have been widely studied globally. This study assessed the QOL of 108 women with PCOS, examining both physical and mental symptoms. Participants completed the Short Form-12 (SF-12) questionnaire through a web-based survey to evaluate their QOL scores. Common symptoms included menstrual irregularity (73.14%), hirsutism (65.7%), acne (62.03%), and obesity (22.22%). Complications such as diabetes mellitus (12.9%), hypertension (2.78%), infertility (1.85%), miscarriages (31.4%), hyperandrogenism (68.51%), and insulin resistance (28.7%) were reported. Patients with infertility had the lowest physical scores (PCS), while those working night shifts had the lowest mental scores (MCS). PCOS significantly affects QOL, with infertility contributing to the lowest physical scores and night shift work correlating with the lowest mental scores. These findings emphasize the need for integrated psychological and physical care, particularly for young working women with PCOS.

Insulin resistant diabetes mellitus in a girl with mild Rabson-Mendenhall syndrome: efficacy of sodium glucose co-transporter 2 inhibitor

Insulin resistant diabetes mellitus in a girl with mild Rabson-Mendenhall syndrome: efficacy of sodium glucose co-transporter 2 inhibitor

Early continuous glucose monitoring-derived glycemic patterns are associated with subsequent insulin resistance and gestational diabetes mellitus development during pregnancy

BackgroundGestational diabetes mellitus (GDM) and insulin resistance (IR) increase the risk of adverse pregnancy outcomes. We aimed to examine the relationship of interstitial glucose assessed by continuous glucose monitoring (CGM) at early gestation, and the subsequent development of IR and GDM, and to determine 24-h interstitial glucose centile distributions in women with normal (non-IR and non-GDM) and suboptimal glycemic status (IR and/or GDM).MethodsCGM measurements were taken for 3–10 days at 18–24 weeks’ gestation, followed by fasting serum insulin and oral glucose tolerance testing at 24–28 weeks’ gestation. IR and GDM were determined by the updated Homeostasis Model Assessment of IR score of ≥ 1.22 and 2013 World Health Organization criteria, respectively. Risks of IR and GDM were estimated using modified Poisson models, and hourly interstitial glucose centiles determined using Generalized Additive Models for Location, Scale and Shape.ResultsThis prospective cohort study involved 167 pregnant women in Singapore, with a mean age of 31.7 years, body mass index of 22.9 kg/m2, and gestation of 20.3 weeks. 25% of women exhibited IR and 18% developed GDM. After confounders adjustment, women with suboptimal glycemic control, indicated by higher mean daily glucose (risk ratio 1.42; 95% confidence interval 1.16, 1.73), glucose management indicator (1.08; 1.03, 1.12), and J-index (1.04; 1.02, 1.06), as well as those with greater glycemic variability, indicated by higher standard deviation (1.69; 1.37, 2.09), coefficient of variation (1.03; 1.00, 1.06), and mean amplitude of glycemic excursions (1.4; 1.14, 1.35) derived from CGM in early gestation were associated with higher risks of developing IR in later gestation. These associations were similarly observed for the development of GDM. Centile curves showed that, compared to those with normal glycemic status, women with suboptimal glycemic status had higher glucose levels, with greater fluctuations throughout 24 h.ConclusionsIn pregnant women who subsequently developed IR and GDM, interstitial glucose levels assessed by CGM were elevated and varied greatly. This supports the potential use of CGM to screen for glycemic changes early in pregnancy.

The effect of the endothelin receptor antagonist atrasentan on insulin resistance in phenotypic clusters of patients with type 2 diabetes and chronic kidney disease.

Type 2 diabetes (T2D) patients with a clinical phenotype characterized by a high degree of insulin resistance are at increased risk of chronic kidney disease (CKD). We previously demonstrated that the endothelin receptor antagonist (ERA) atrasentan reduced insulin resistance in T2D. In this study, we compared the effect of atrasentan on insulin resistance across different phenotypic clusters of patients with T2D. We performed a post hoc analysis of the SONAR trial, a randomized, placebo-controlled trial of the ERA atrasentan in patients with T2D and CKD. Patients were stratified into four previously identified phenotypic clusters: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). Changes in insulin resistance, assessed by HOMA-IR, were compared between the phenotypic clusters using a mixed effects model. In total, 931 patients were included in the analysis. In the overall population, atrasentan compared to placebo reduced HOMA-IR by 12.9% [95%CI 3.5,21.4]. This effect of atrasentan was more pronounced in clusters characterized by insulin resistance or deficiency: (SIRD cluster 26.2% [95% CI 3.8,43.3] and SIDD cluster 18.5% [95%CI -3.8,35.9]), although the latter did not reach statistical significance. The effect of atrasentan compared to placebo was less pronounced in the other two clusters (MARD 12.2% [95% CI -1.7,24.12] and MOD -5.3% [95% CI -28.9,13.9]). Atrasentan significantly improved insulin sensitivity in patients with T2D and CKD, especially in those characterized by high insulin resistance (SIRD cluster). Further studies are warranted to investigate the long-term clinical outcomes of atrasentan treatment in these distinct phenotypic clusters.

Insulin Resistance and Impaired Insulin Secretion Predict Incident Diabetes: A Statistical Matching Application to the Two Korean Nationwide, Population-Representative Cohorts.

To evaluate whether insulin resistance and impaired insulin secretion are useful predictors of incident diabetes in Koreans using nationwide population-representative data to enhance data privacy. This study analyzed the data of individuals without diabetes aged >40 years from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2010 and 2015 and the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Owing to privacy concerns, these databases cannot be linked using direct identifiers. Therefore, we generated 10 synthetic datasets, followed by statistical matching with the NHIS-HEALS. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were used as indicators of insulin resistance and insulin secretory function, respectively, and diabetes onset was captured in NHIS-HEALS. A median of 4,580 (range, 4,463 to 4,761) adults were included in the analyses after statistical matching of 10 synthetic KNHANES and NHIS-HEALS datasets. During a mean follow-up duration of 5.8 years, a median of 4.7% (range, 4.3% to 5.0%) of the participants developed diabetes. Compared to the reference low-HOMA-IR/high-HOMA-β group, the high-HOMA-IR/low- HOMA-β group had the highest risk of diabetes, followed by high-HOMA-IR/high-HOMA-β group and low-HOMA-IR/low- HOMA-β group (median adjusted hazard ratio [ranges]: 3.36 [1.86 to 6.05], 1.81 [1.01 to 3.22], and 1.68 [0.93 to 3.04], respectively). Insulin resistance and impaired insulin secretion are robust predictors of diabetes in the Korean population. A retrospective cohort constructed by combining cross-sectional synthetic and longitudinal claims-based cohort data through statistical matching may be a reliable resource for studying the natural history of diabetes.

Andrographis paniculata improves glucose regulation by enhancing insulin sensitivity and upregulating GLUT 4 expression in Wistar rats.

Although the hypoglycaemic effect of Andrographis paniculata (Burm.f.) Nees [Acanthaceae] has been documented, reports on its effect in an apparently healthy state are limited. This study investigated whether or not A. paniculata exerts hypoglycaemic effect in a non-diabetic state. It also explored the impact of A. paniculata on glycolytic enzymes and GLUT 4 protein expression, as a possible mode of action. Twenty male Wistar rats were randomly assigned into two groups (n = 10 rats/group). The control rats were vehicle-treated (0.5 ml of distilled water), while the A. paniculata-treated rats had 500 mg/kg of A. paniculata per os once daily for 35 days. A. paniculata treatment led to improved insulin sensitivity evidenced by increased HOMA-β (88.08 ± 2.13 vs. 120.80 ± 1.52, p < 0.0001), HOMA-S (283.60 ± 8.82 vs. 300.50 ± 9.30, p = 0.0189), and reduced TyG index (4.22 ± 0.04 vs. 3.95 ± 0.07, p < 0.0002) and HOMA-IR (0.32 ± 0.01 vs. 0.25 ± 0.01, p < 0.0001) when compared with the control. It also improved glucose regulation as depicted by reduced fasting blood glucose (3.77 ± 0.10 vs. 3.24 ± 0.11, p < 0.0001) and glycated hemoglobin (HbA1c; 7.69 ± 1.15 vs. 5.95 ± 0.82, p = 0.0245), and atherogenic dyslipidaemia, including AIP (-0.12 ± 0.03 vs. -0.26 ± 0.03, p < 0.0001) and CRI-I (2.70 ± 0.29 vs. 1.84 ± 0.27, p < 0.0001). These findings were accompanied by enhanced hepatic and muscular redox state, increased activities of glycolytic enzymes, upregulated GLUT 4 (0.80 ± 0.27 vs. 6.20 ± 0.84, p < 0.0001), and increased circulating nitric oxide (5.45 ± 0.24 vs. 6.79 ± 0.33, p = 0.0002). A. paniculata exerts positive effect on glucose metabolism and utilization by improving insulin sensitivity and upregulating the activities of glycolytic enzymes and GLUT 4 protein expression. This implies that A. paniculata may be beneficial in preventing insulin resistance and incident diabetes. Nonetheless, it should be used with caution to prevent hypoglycaemia in a non-diabetic state.

Identification of new phenotypes in type 2 diabetes with acute myocardial infarction: toward a precision medicine?

Abstract Background Type 2 diabetes mellitus (T2DM) is a highly heterogeneous entity, with multiple subgroups differing by clinic presentation, disease progression and risk of complications such as myocardial infarction (MI). A new T2DM phenotyping classification has been recently proposed to help to improve treatment tailoring and target early treatments, and we aimed to identify the prevalence and characteristics of the new phenotypes. Methods All consecutive adults with a history T2DM hospitalized in a french Coronary Intensive Care Unit for an acute MI between February 1st, 2021 and January 31st, 2023 were included. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance). We stratified patients into five subgroups : 1/ SAID=severe autoimmune diabetes; 2/ SIDD=severe insulin-deficient diabetes; 3/ SIRD=severe insulin-resistant diabetes; 4/ MOD=mild obesity-related diabetes; and 5/ MARD=mild age-related diabetes. Results Among the 266 patients included, characteristics according to diabetes phenotypes are summarized in the Table. Conclusions Our prospective study showed that in real-world T2DM patients with acute MI, unclassical phenotypes, i.e. hyperinsulinaemic and insulinopaenic were common. Given the large discrepancies in characteristics, our findings suggest the relevance of the new substratification. However, its clinical utlity and translation in tailored treatment strategies and prognosis remains to be determined.Table.

Relationship of Plasma Apolipoprotein C-I Truncation With Risk of Diabetes in the Multi-Ethnic Study of Atherosclerosis and the Actos Now for the Prevention of Diabetes Study.

Higher truncated-to-native apolipoprotein (apo) C-I proteoform ratios (C-I'/C-I) are associated with favorable cardiometabolic risk profiles, but their relationship with longitudinal changes in insulin resistance (IR) and incident diabetes is unknown. Plasma apoC-I proteoforms were measured by mass spectrometry immunoassay at baseline in 4,742 nondiabetic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 524 participants with prediabetes in the Actos Now for Prevention of Diabetes (ACT NOW) study. The primary outcome was incident diabetes (fasting glucose [FG] ≥7.0 mmol/L or hypoglycemic medication use in MESA; FG ≥7.0 mmol/L or 2-h glucose ≥11.1 mmol/L in an oral glucose tolerance test [OGTT] in ACT NOW). Secondary outcomes were changes in FG and HOMA-IR in MESA, and OGTT-glucose area under the curve (AUCglucose) and Matsuda insulin sensitivity index (ISI) in ACT NOW. In MESA, a higher C-I'/C-I was associated with lower risk of diabetes (n = 564 events; HR 0.87 [95% CI 0.79, 0.95] per SD; P = 0.0036; median follow-up, 9 years), and smaller increases (follow-up adjusted for baseline) in FG (-0.5%; P < 0.0001) and HOMA-IR (-2.9%; P = 0.011) after adjusting for baseline clinical and demographic covariates, including plasma triglycerides and HDL cholesterol. Total apoC-I concentrations were not associated with changes in FG, HOMA-IR, or incident diabetes. In ACT NOW, higher C-I'/C-I was associated with smaller increases in AUCglucose (-1.8%; P = 0.0052), greater increases in ISI (7.2%; P = 0.0095), and lower risk of diabetes (n = 59 events; 0.66 [95% CI 0.48, 0.91]; P = 0.004; median follow-up, 2.5 years) after adjusting for treatment group and diabetes risk factors, including plasma lipids. Our results indicate that apoC-I truncation may contribute to changes in glucose levels, IR, and risk of diabetes.

Depression symptoms, wellbeing, health-related quality of life, and diabetes-related distress in novel subtypes of recent-onset diabetes in Germany: a 5-year observational follow-up study

The subjective experiences of individuals living with diabetes is commonly assessed with patient-reported outcomes (PROs; eg, depression symptoms, wellbeing, health-related quality of life [HRQOL], and diabetes-related distress). Cluster analyses have identified novel diabetes subtypes differing in phenotypic and metabolic characteristics. We aimed to investigate associations between these subtypes and PROs and whether subtype predicted PROs 5 years later. Baseline (<12 months after a diabetes diagnosis) and 5-year follow-up data were collected from German Diabetes Study (GDS) participants. Multiple regressions were applied to analyse associations between diabetes subtypes and depression symptoms (Center for Epidemiologic Studies Depression Scale), wellbeing (WHO-5), HRQOL (SF-36), and diabetes-related distress (Problem Areas in Diabetes Scale). Cluster analyses at baseline (n=1391) identified participants with severe autoimmune diabetes (SAID, 417 [30%]), severe insulin-deficient diabetes (SIDD, 33 [2%]), severe insulin-resistant diabetes (SIRD, 150 [11%]), mild obesity-related diabetes (MOD, 354 [25%]), and mild age-related diabetes (MARD, 437 [31%]). At baseline, multiple regression analyses showed that participants with SIRD had higher depression symptoms than participants with MARD and lower physical HRQOL than all other subtypes. Participants with SAID reported higher depression symptoms and lower mental HRQOL than participants with MARD, higher physical HRQOL than participants with MARD and MOD, and higher diabetes-related distress than most other subtypes. At the 5-year follow-up, clustering predicted no statistically significant changes in PROs after adjustment for multiple testing, whereas descriptive analyses demonstrated that individuals with SIRD were more likely to experience clinically relevant depression symptoms (16% vs 6%) and low wellbeing (31% vs 14%), respectively, than individuals with MARD. Diabetes subtypes already differ in PROs at diabetes diagnosis. Our analyses had limited predictive power during follow-up. However, our findings suggest that clustering could predict future changes in depression symptoms. The GDS was initiated and financed by the German Diabetes Center, which is funded by the German Federal Ministry of Health, the Ministry of Culture and Science of the state of North Rhine-Westphalia, and by the German Federal Ministry of Education and Research to the German Center for Diabetes Research. For the German translation of the abstract see Supplementary Materials section.

Glucagon and glucagon-like peptide-1 dual agonist therapy: A possible future towards fatty kidney disease.

Obesity is a growing epidemic affecting approximately 40% of the adult population in developed countries with major health consequences and comorbidities, including diabetes mellitus and insulin resistance, metabolically associated fatty liver disease, atherosclerotic cardiovascular and cerebrovascular diseases and chronic kidney disease. Pharmacotherapies targeting significant weight reduction may have beneficial effects on such comorbidities, though such therapeutic options are highly limited. In this narrative review, we aim to evaluate current knowledge regarding dual agonist therapies and potential implications for managing fatty kidney and chronic kidney disease. Glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors are two novel classes of glucose-lowering medications with potential implications and beneficiary effects on renal outcomes, including estimated glomerular filtration rate, albuminuria and chronic kidney disease progression. Recently, dual agonist therapies targeting glucagon-like peptide-1 and glucagon receptors, namely survodutide and cotadutide, have been evaluated in managing metabolically associated fatty liver disease, a well-established example of visceral obesity. Fatty kidney is another novel concept implicated in the pathophysiology of chronic kidney disease among patients with visceral obesity.

Superior metabolic improvement of polycystic ovary syndrome traits after GLP1-based multi-agonist therapy

Polycystic ovary syndrome (PCOS) is a heterogeneous condition, defined by oligo-/anovulation, hyper-androgenism and/or polycystic ovaries. Metabolic complications are common in patients suffering PCOS, including obesity, insulin resistance and type-2 diabetes, which severely compromise the clinical course of affected women. Yet, therapeutic options remain mostly symptomatic and of limited efficacy for the metabolic and reproductive alterations of PCOS. We report here the hormonal, metabolic and gonadal responses to the glucagon-like peptide-1 (GLP1)-based multi-agonists, GLP1/Estrogen (GLP1/E), GLP1/gastric inhibitory peptide (GLP1/GIP) and GLP1/GIP/Glucagon, in two mouse PCOS models, with variable penetrance of metabolic and reproductive traits, and their comparison with metformin. Our data illustrate the superior efficacy of GLP1/E vs. other multi-agonists and metformin in the management of metabolic complications of PCOS; GLP1/E ameliorates also ovarian cyclicity in an ovulatory model of PCOS, without direct estrogenic uterotrophic effects. In keeping with GLP1-mediated brain targeting, quantitative proteomics reveals changes in common and distinct hypothalamic pathways in response to GLP1/E between the two PCOS models, as basis for differential efficiency. Altogether, our data set the basis for the use of GLP1-based multi-agonists, and particularly GLP1/E, in the personalized management of PCOS.

Role of patatin-like phospholipase domain-containing 3 gene for decreasing kidney function in recently diagnosed diabetes mellitus

AimsWe examined the association of the G allele in the single-nucleotide polymorphism (SNP) rs738409 in the third exon of patatin-like phospholipase domain-containing 3 gene (PNPLA3) gene, with chronic kidney disease in diabetes endotypes. MethodsParticipants with recent-onset diabetes (n = 707) from the prospective German Diabetes Study (GDS) underwent cluster assignment, detailed phenotyping, genotyping and magnetic resonance spectroscopy to quantify hepatocellular lipid content (HCL). ResultsSevere insulin-resistant diabetes (SIRD) had the lowest glomerular filtration rates (eGFR) and highest HCL compared to severe insulin-deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes endotypes (all p < 0.05). HCL was negatively associated with eGFR (r = −0.287, p < 0.01) across all groups. Stratification by G-allele carrier status did not reveal any association between HCL and eGFR among the endotypes. However, the proportion of G-allele carriers increased from 44 % for eGFR >60 ml/min to 52 % for eGFR <60 ml/min (p < 0.05). ConclusionsThe PNPLA3 polymorphism may contribute to declining kidney function independently of liver lipids.

Management Strategies for Obese Diabetes

In recent years, there has been a growing emphasis on the relationship between obesity and diabetes. An analysis of Korean data revealed that more than 75% of diabetic patients were overweight or obese, with two-thirds having abdominal obesity. Traditional treatment goals for diabetes have primarily focused on lowering blood glucose levels to prevent and treat microvascular and macrovascular complications, which is known as the glucocentric approach. However, with the recognition of the shared pathophysiology of insulin resistance in both diabetes and obesity, a weight-centric approach has emerged, particularly beneficial for patients in whom insulin resistance is a primary driver of type 2 diabetes. Of note, the overlap of various physiological aspects in diabetic patients necessitates a multicentric approach for effective type 2 diabetes management. Recent guidelines now recommend weight loss as a primary treatment goal alongside blood glucose control for overweight and obese diabetic patients, highlighting the significance of weight management in diabetes care. Medications such as glucagon-like peptide-1 (GLP-1) receptor agonist or dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist with weight-loss effects are recommended for this patient population. Ongoing research is exploring the potential of various gut hormone-based therapies, offering hope for effective weight management and improved diabetes outcomes in the growing population of obese diabetic individuals.

Identifying subtypes of type 2 diabetes mellitus based on real-world electronic medical record data in China

AimsTo replicate the European subtypes of type 2 diabetes mellitus (T2DM) in the Chinese diabetes population and investigate the risk of complications in different subtypes. MethodsA diabetes cohort using real-world patient data was constructed, and clustering was employed to subgroup the T2DM patients. Kaplan–Meier analysis and the Cox models were used to analyze the association between diabetes subtypes and the risk of complications. ResultsA total of 2,652 T2DM patients with complete clustering data were extracted. Among them, 466 (17.57 %) were classified as severe insulin-deficient diabetes (SIDD), 502 (18.93 %) as severe insulin-resistant diabetes (SIRD), 672 (25.34 %) as mild obesity-related diabetes (MOD), and 1,012 (38.16 %) as mild age-related diabetes (MARD). The risk of chronic kidney disease (CKD) and diabetic retinopathy (DR) were different in the four subtypes. Compared with MARD, SIRD had a higher risk of CKD (HR 2.40 [1.16, 4.96]), and SIDD had a higher risk of DR (HR 2.16 [1.11, 4.20]). The risk of stroke and coronary events had no difference. ConclusionsThe European T2DM subtypes can be replicated in the Chinese diabetes population. The risk of CKD and DR varied among different subtypes, indicating that proper interventions can be taken to prevent specific complications in different subtypes.

Type 2 Diabetes Subtypes and Their Role in Metabolic Liver Disease and Fibrosis Progression.

BACKGROUND The relationship between different subgroups of type 2 diabetes (T2D) and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis has not been thoroughly studied. This study aims to determine the association between T2D subgroups and the risk of developing advanced liver fibrosis using the Fibrosis-4 (FIB-4) index, a non-invasive marker for assessing liver fibrosis risk. MATERIAL AND METHODS A total of 1205 patients with T2D were categorized into 4 distinct subgroups: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). The FIB-4 index was calculated for each patient to estimate the degree of liver fibrosis, with the following cutoff points: <1.3 indicating no or mild fibrosis, 1.3-2.67 suggesting moderate fibrosis, and >2.67 indicating advanced fibrosis (F3-F4). Logistic regression was used to compare the odds of advanced fibrosis across these subgroups. RESULTS The SIRD subgroup exhibited significantly higher odds of advanced liver fibrosis (F3-F4), compared with the other subgroups, as indicated by elevated FIB-4 scores (P<0.05). In contrast, the SIDD and MOD subgroups had lower odds of advanced fibrosis, while the MARD subgroup showed an intermediate association. CONCLUSIONS The findings suggest that the FIB-4 index, as a noninvasive assessment tool, effectively stratifies liver fibrosis risk among different T2D subgroups. This stratification can inform more personalized management strategies for patients with MASLD, underscoring the importance of accounting for the heterogeneity within T2D in clinical assessments of liver fibrosis risk.

The relation of mTOR with diabetic complications and insulin resistance in patients with type 2 diabetes mellitus

BackgroundDysregulation of the mechanistic target of rapamycin (mTOR) has been related to several metabolic conditions, notably obesity and type 2 diabetes (T2DM). This study aimed to evaluate the role of mTOR in patients with T2DM, and its relationship with insulin resistance and microvascular complications.MethodsThis case-control study was conducted on 90 subjects attending the Outpatient Internal Medicine Clinic in Damanhur Teaching Hospital. Subjects were divided into 3 groups, Group I: 20 healthy controls, Group II: 20 subjects with T2DM without complications, and Group III: 50 subjects with T2DM with microvascular complications. An Enzyme-linked immunosorbent assay was used to measure serum mTOR levels. T2DM and diabetic complications were defined according to the diagnostic criteria of the American Diabetes Association.ResultsThe results revealed significant positive correlations to HbA1c (r = 0.530, P < 0.001), fasting glucose (r = 0.508, P < 0.001), and HOMA- IR (r = 0.559, P < 0.001), and a significant negative correlation to eGFR (r=-0.370, P = 0.002). Multivariate analysis revealed an independent association of mTOR and HbA1c values with the presence of microvascular complications. The prediction of microvascular complications was present at a cutoff value of 8 ng/ml mTOR with a sensitivity of 100% and specificity of 95% with an AUC of 0.983 and a p-value < 0.001.ConclusionmTOR is a prognostic marker of diabetic microvascular and is associated with insulin resistance in patients with T2DM.Trial RegistrationThe study was conducted following the Declaration of Helsinki, and approved by the Ethics Committee of Alexandria University (0201127, 19/7/2018).

Clinical application of cluster analysis in patients with newly diagnosed type 2 diabetes.

Early prevention and treatment of type 2 diabetes mellitus (T2DM) is still a huge challenge for patients and clinicians. Recently, a novel cluster-based diabetes classification was proposed which may offer the possibility to solve this problem. In this study, we report our performance of cluster analysis of individuals newly diagnosed with T2DM, our exploration of each subtype's clinical characteristics and medication treatment, and the comparison carried out concerning the risk for diabetes complications and comorbidities among subtypes by adjusting for influencing factors. We hope to promote the further application of cluster analysis in individuals with early-stage T2DM. In this study, a k-means cluster algorithm was applied based on five indicators, namely, age, body mass index (BMI), glycosylated hemoglobin (HbA1c), homeostasis model assessment-2 insulin resistance (HOMA2-IR), and homeostasis model assessment-2 β-cell function (HOMA2-β), in order to perform the cluster analysis among 567 newly diagnosed participants with T2DM. The clinical characteristics and medication of each subtype were analyzed. The risk for diabetes complications and comorbidities in each subtype was compared by logistic regression analysis. The 567 patients were clustered into four subtypes, as follows: severe insulin-deficient diabetes (SIDD, 24.46%), age-related diabetes (MARD, 30.86%), mild obesity-related diabetes (MOD, 25.57%), and severe insulin-resistant diabetes (SIRD, 20.11%). According to the results of the oral glucose tolerance test (OGTT) and biochemical indices, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hBG), HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride-glucose index (TyG) were higher in SIDD and SIRD than in MARD and MOD. MOD had the highest fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP), fasting insulin (FINS), 2-hour postprandial insulin (2hINS), serum creatinine (SCr), and uric acid (UA), while SIRD had the highest triglycerides (TGs) and TyG-BMI. Albumin transaminase (ALT) and albumin transaminase (AST) were higher in MOD and SIRD. As concerms medications, compared to the other subtypes, SIDD had a lower rate of metformin use (39.1%) and a higher rate of α-glucosidase inhibitor (AGI, 61.7%) and insulin (74.4%) use. SIRD showed the highest frequency of use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i, 36.0%) and glucagon-like peptide-1 receptor agonists (GLP-1RA, 19.3%). Concerning diabetic complications and comorbidities, the prevalence of diabetic kidney disease (DKD), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and hypertension differed significantly among subtypes. Employing logistic regression analysis, after adjusting for unmodifiable (sex and age) and modifiable related influences (e.g., BMI, HbA1c, and smoking), it was found that SIRD had the highest risk of developing DKD (odds ratio, OR = 2.001, 95% confidence interval (CI): 1.125-3.559) and dyslipidemia (OR = 3.550, 95% CI: 1.534-8.215). MOD was more likely to suffer from NAFLD (OR = 3.301, 95%CI: 1.586-6.870). Patients with newly diagnosed T2DM can be successfully clustered into four subtypes with different clinical characteristics, medication treatment, and risks for diabetes-related complications and comorbidities, the cluster-based diabetes classification possibly being beneficial both for prevention of secondary diabetes and for establishment of a theoretical basis for precision medicine.