May 2026· BMJ Open Diabetes Research & Care· Vol 14, pp. e005653· 0 citations· 41 references
Medicine
TL;DR
In T2DM, impaired glucagon suppression during OGTT is associated with insulin resistance closely, highlighting insulin resistance as a key factor in alpha-cell dysfunction.
Abstract
Abstract Introduction This study examined how insulin resistance and impaired insulin secretion are associated with hyperglucagonemia during oral glucose tolerance tests (OGTT) in type 2 diabetes mellitus (T2DM). Research design and methods A retrospective analysis included 247 patients with T2DM treated at Tianjin Medical University General Hospital from October 2022 to March 2025. All underwent a 75 g OGTT, with blood samples collected at 0, 0.5, 1, 2, and 3 hours for glucose, insulin, C-peptide, and glucagon measurement. Insulin resistance was assessed via homeostasis model assessment of insulin resistance (HomaIR) and C-peptide immunoreactivity insulin resistance (CPRIR), while insulin secretion was evaluated using C-peptide area under the curve (AUCcp), homeostasis model assessment of beta cell function (HomaB), first-phase and second-phase insulin secretion during OGTT (first PH and second PH). Generalized linear models and mediation analyses examined associations between glucagon levels and above indices. Model fitness and robustness were evaluated via residual diagnostics, Cook’s distance, and bootstrapped CIs. Results Glucagon levels during the OGTT were significantly elevated in patients with severe insulin resistance (HomaIR Q3 and CPRIR Q1), even after adjusting for confounders. In contrast, groups with the poorest insulin secretion (AUCcp Q1, HomaB Q1, first PH Q1, and second PH Q1) did not show elevated glucagon levels compared with those with better secretion. Mediation analysis confirmed that neither AUCcp nor HomaB mediated the relationship between insulin resistance and glucagon levels. Residual diagnostics demonstrated a satisfactory model fit. Furthermore, sensitivity analyses, both by excluding influential points identified via Cook’s distance and by applying bootstrapped CIs, yielded consistent results, thereby affirming the robustness of the model. Conclusions In T2DM, impaired glucagon suppression during OGTT is associated with insulin resistance closely, highlighting insulin resistance as a key factor in alpha-cell dysfunction.
C-peptide can be used as an appropriate index for identifying IR in T2DM patients with complications and illustrated the clinical utility of C-peptide in microvascular complications such as diabetic nephropathy and diabetic retinopathy.
K. Siddiqui, S. Joy, S. Nawaz et al.· Medicine· 0 citations
Background: Type 2 diabetes mellitus (T2DM) is one of the most common chronic metabolic diseases worldwide, and insulin resistance is the core pathophysiological basis for its development. This study aims to explore the relationship between various metabolic-related indicators and insulin resistance in patients with T2DM, and to analyze the correlation between obesity indicators, glucose and lipid metabolism indicators, and serum uric acid with insulin resistance, providing a reference for clinical identification of insulin resistance.Methods: This was a single-center retrospective study, consecutively enrolling 263 patients with type 2 diabetes who received treatment at our center between August 2022 and August 2025. Patients were divided into a non-insulin-resistant group (n = 211) and an insulin-resistant group (n = 52) based on the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Baseline clinical data and laboratory parameters were collected, including body mass index, waist-to-hip ratio, fasting blood glucose, 2-hour postprandial blood glucose, lipid profile, glycated hemoglobin, fasting C-peptide, and serum uric acid. The triglyceride-glucose (TyG) index was also calculated. Logistic regression analysis was performed to screen for metabolic indicators associated with insulin resistance, and receiver operating characteristic (ROC) curve analysis was then conducted to evaluate the discriminative ability of these indicators for insulin resistance.Results: Patients in the insulin resistance group had significantly higher levels of body mass index (BMI), waist-to-hip ratio (WHR), triglycerides, fasting blood glucose, TyG index, fasting C-peptide, glycated hemoglobin (HbA1c), systolic blood pressure, diastolic blood pressure, and serum uric acid than the non-insulin resistance group (all p < 0.05), and a higher proportion of patients with hypertension (65.38% vs. 46.45%, p = 0.014). Multivariate logistic regression analysis showed that WHR, TyG index, fasting C-peptide, and serum uric acid were independently associated with insulin resistance. The area under the curve (AUC) for assessing insulin resistance using the combined indicators was 0.81 (95% CI: 0.74–0.88), with a sensitivity of 79.0% and a specificity of 71.0%.Conclusion: In patients with type 2 diabetes, WHR and serum uric acid levels are significantly correlated with insulin resistance status. These indicators reflect various metabolic characteristics from different perspectives, including obesity, glucose and lipid metabolism, and pancreatic β-cell function, and may provide preliminary insights into the metabolic abnormalities associated with insulin resistance in patients with type 2 diabetes.
Findings indicate significant changes in the IGF system in patients with T1D, and changes in IGF-1 and IGF-2 levels are thought to be related to the metabolic disturbances seen in T1D.
E. M. Eltayef, K. Gharab, L. Ghannawi et al.· Diabetes mellitus· 0 citations
Vitamin D deficiency is an increasingly recognized yet poorly addressed metabolic risk factor that may aggravate insulin resistance in patients with type 2 diabetes mellitus (T2DM), thereby worsening glycemic control and long-term outcomes. Therefore, it is of interest to examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and markers of insulin resistance including the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), fasting insulin, fasting blood glucose and HbA1c in 120 patients with confirmed T2DM. Serum vitamin D levels were significantly lower in patients with higher HOMA-IR values, with a strong inverse correlation observed between serum vitamin D and HOMA-IR (r = −0.72, p<0.001). The prevalence of insulin resistance (HOMA-IR >2.5) was 92.9% in severely deficient patients compared to 20.0% in those with sufficient vitamin D levels. Thus, data shows the clinical importance of routine vitamin D assessment in T2DM patients as a potentially modifiable target to reduce insulin resistance and improve glycemic outcomes.
Background and objective: Diabetes Mellitus type 2 (T2DM) represents a serious risk to public health known as hyperglycemia. High levels of serum leucine a branched chain amino acid have been associated with early insulin resistance and metabolic imbalances. This study investigates the relationship between serum leucine levels and insulin resistance, and to evaluate its potential as a biomarker alongside standard blood sugar markers in diabetic, prediabetic, and leucine-supplemented individuals undergoing training.
Methods: A cross-sectional study, conducted at the (Galiawa hospital for diabetes and endocrinology and (AKA Fitness) center)/ Erbil city / Iraq. A total of 155 participants, aged between 30 and 69, were included, composed of 46 with T2DM, 38pre-diabetic patients, 36 non-diabetic and 35 healthy young active training individuals who received leucine supplementation. Data was collected by interview questionnaire about; sociodemographic, life style and results of biochemical tests.
Results: High levels of serum Leucine were significantly increase with age, obesity (OR=2.4, 95% CI. 1.7 - 2.8) and increased risk of high fasting blood sugar (OR=1.14,95% of CI 1.09-1.18), HbA1c (OR=1.24, 95% of CI 1.12-1.37), and insulin resistance (OR= 1.06, 95% of CI 1.02-1.1) in diabetic and prediabetic. Excessive supplementation caused excess serum leucine levels and increase potential insulin resistance (OR=1.3, 95% CI I,07-1.6) with advancing age.
Conclusion: High serum leucine levels can cause insulin resistance in elderly, obese, prediabetic, and diabetic patients, suggesting its potential use as a biomarker for early diagnosis. A low dose of leucine supplementation should be considered in individuals undergoing training.
Asmaa Omar, Jwan Jewzali· Zanco Journal of Medical Sci...· 0 citations
Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia due to insufficient insulin production or the body’s poor response to insulin (insulin resistance). Amino acids are closely associated with glucose dysregulation, and disturbances of amino acid metabolism may break the balance of muscle breakdown, protein synthesis, and overactivation of gluconeogenesis, which precedes the onset of T2DM. Aim of Study This study was designed to identify the levels of nonessential amino acids in recently developed T2DM patients, which may help in the early diagnosis of the disease. Methods The 180 individuals who participated in this study were categorized as healthy controls, prediabetes, and T2DM. Tests conducted for each participant included glucose using enzymatic methods, HbA1c and nonessential amino acids using ion‐exchange high‐performance liquid chromatography (HPLC); and insulin using a sandwich‐based electrochemiluminescence immunoassay (ECLIA). Insulin resistance was calculated using the HOMA‐IR formula. Results Newly diagnosed T2DM patients had increased alanine, asparagine, aspartate, glutamate, and proline but decreased serine, arginine, cystine, glutamine, and glycine levels. Amino acid levels varied by obesity status, with alanine, aspartate, and serine rising with obesity, while asparagine, glutamate, arginine, and glycine decreased. Alanine, aspartate, and serine correlated positively with BMI, insulin, and HOMA‐IR, whereas asparagine, glutamate, and arginine showed negative correlations. Cystine and glycine correlated negatively with age. Strong positive and negative interrelationships existed among these amino acids. Conclusion The study revealed that newly diagnosed T2DM and prediabetes are associated with increased levels of certain nonessential amino acids (alanine, asparagine, aspartate, glutamate, proline) and decreased serine, arginine, cystine, glutamine, and glycine compared to healthy controls. These amino acid levels were influenced by obesity and correlated with insulin resistance and BMI. Altered amino acid metabolism plays a role in early T2DM development and could serve as biomarkers for diagnosis and management.
A. A. H. Al-Rubaye, W. E. Jasim, Ahmed A. Mohsin· Journal of Nutrition and Met...· 0 citations