c-peptide and Latent-Autoimmune-Diabetes-in-Adults

The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta-analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients.. We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, β-cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis.. Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference -0.36, 95% confidence interval -0.61 to -0.10, I. Sitagliptin combined with insulin can achieve better glycemic control and improve islet β-cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well-designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Latent Autoimmune Diabetes in Adults; Randomized Controlled Trials as Topic; Sitagliptin Phosphate

The classification of diabetes mellitus in 2020 still starts with 2 major types, ie, type 1 and type 2, but each of these now includes a few uncommon variants. Understanding the many faces of the diabetes syndrome can make a difference in how clinicians select glucose-lowering therapy.

Topics: Autoantibodies; Biomarkers; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Latent Autoimmune Diabetes in Adults; Phenotype

Latent Autoimmune Diabetes in the Adult, LADA has been investigated less than "classical" type 1 and type 2 diabetes and the criteria for and the relevance of a LADA diagnosis have been challenged. Despite the absence of a genetic background that is exclusive for LADA this form of diabetes displays phenotypic characteristics that distinguish it from other forms of diabetes. LADA is heterogeneous in terms of the impact of autoimmunity and lifestyle factors, something that poses problems to therapy and follow-up, perhaps particularly in those with marginal positivity. Yet, there appears to be clear clinical utility in classifying individuals as LADA.

Topics: Adult; Age of Onset; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Humans; Islets of Langerhans; Latent Autoimmune Diabetes in Adults

Cytokines and chemokines participate in autoimmune processes at cellular targets which include insulin-producing beta cells. To which extent such participation is reflected in the circulation has not been conclusively resolved.. We compared the time course of cytokines/chemokines in Latent Autoimmune Diabetes in Adults (LADA) patients heterogeneous for high or low autoimmune activity as determined by levels of antibodies against glutamic acid decarboxylase (GADA).. Serum samples to be measured were from a two-armed randomized controlled trial (RCT) in 68 LADA patients. The study encompassed 21 months with C-peptide as primary endpoint. We measured 27 immune mediators at baseline, at 9 and at 21 months (end of study). Results of measurements were analyzed by multiple linear regression.. In LADA, high levels of GADA, a proxy for high autoimmune activity and linked to a decline in C-peptide, was associated with a decrease of selected cytokines over time. This implies that the decline of IL-1ra and IL-1 beta in the circulation reflects autoimmune activity and beta cell demise in LADA.

Topics: Adult; Autoantibodies; C-Peptide; Cytokines; Female; Glutamate Decarboxylase; Humans; Interleukin-1beta; Latent Autoimmune Diabetes in Adults; Male

To assess the efficacy and tolerability of saxagliptin and C-peptide secretion in patients with diagnosed type 2 diabetes classified as glutamic acid decarboxylase antibody (GADA)-positive or GADA-negative.. Post hoc analysis of data pooled from five randomized, placebo-controlled, 24-week phase 3 studies (n = 2709) was conducted. We evaluated mean change from baseline at week 24 in HbA1c , fasting plasma glucose, postprandial plasma glucose, fasting and postprandial C-peptide, and HOMA2-%β and the proportion of patients achieving HbA1c  < 7% (53 mmol/mol) at week 24.. Saxagliptin produced greater adjusted mean reductions from baseline in HbA1c versus placebo for GADA-negative [difference vs placebo (95% CI), -0.62% (-0.71% to -0.54%); -6.8 mmol/mol (-7.8, -5.9)] and GADA-positive patients [-0.64% (-1.01% to -0.27%); -7.0 mmol/mol (-11.0, -3.0)]. Consistently, saxagliptin produced a greater reduction from baseline in fasting plasma glucose and postprandial plasma glucose versus placebo in GADA-positive versus GADA-negative patients, and more patients achieved HbA1c  < 7% (53 mmol/mol) with saxagliptin versus placebo in both GADA-negative and GADA-positive patients. Saxagliptin increased β-cell function as assessed by HOMA2-%β and postprandial C-peptide area under the curve from baseline in patients in both GADA-positive and GADA-negative patients. Adverse events and hypoglycaemic events were similar across treatment groups and GADA categories.. Saxagliptin was effective in lowering blood glucose levels and generally well tolerated in GADA-positive patients. Interestingly, saxagliptin appears to improve β-cell function in these patients, although a longer treatment duration may be needed to confirm this finding.

Topics: Adamantane; Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucose Intolerance; Humans; Latent Autoimmune Diabetes in Adults; Male; Middle Aged; Young Adult

We aimed to investigate whether human leukocyte antigen (HLA) Class I loci differentially modulated the risk for and clinical features of Chinese people with classic type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA).. In this case-control study, genotypes of HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 loci were obtained from 1067 cases with classic T1D, 1062 cases with LADA, and 1107 normal controls using next-generation sequencing.. Despite 4 alleles shared between classic T1D and LADA (protective: A*02:07 and B*46:01; susceptible: B*54:01 and C*08:01), 7 Class I alleles conferred risk exclusively for classic T1D (A*24:02, B*15:02, B*15:18, B*39:01, B*40:06, B*48:01, and C*07:02) whereas only A*02:01 was an additional risk factor for LADA. Class I alleles affected a wide spectrum of T1D clinical features, including positive rate of protein tyrosine phosphatase autoantibody and zinc transporter 8 autoantibody (A*24:02), C-peptide levels (A*24:02), and age at diagnosis (B*46:01, C*01:02, B*15:02, C*07:02, and C*08:01). By contrast, except for the detrimental effect of C*08:01 on C-peptide concentrations in LADA, no other Class I associations with clinical characteristics of LADA could be reported. The addition of Class I alleles refined the risk model consisting only of DR-DQ data in classic T1D while the overall predictive value of the LADA risk model comprising both Class I and II information was relatively low.. The attenuated HLA Class I susceptibility to LADA was indicative of a less deleterious immunogenetic nature compared with classic T1D. These autoimmune diabetes-related Class I variants might serve as additional markers in future screening among Chinese people.

Topics: Adult; Autoantibodies; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; East Asian People; Genetic Predisposition to Disease; Humans; Latent Autoimmune Diabetes in Adults

The objective of this study is to explore the relationship between red blood cell distribution and islet β-cell function indexes in patients with Latent Autoimmune Diabetes in Adults.. A total of 487 LADA patients were enrolled in this cross-sectional study. Patients were divided into three groups according to RDW tertiles. Clinical and laboratory measurements of age, height, weight, duration of diabetes, blood pressure, RDW, glycosylated hemoglobin A1c (HbA1c), C-peptide and blood lipids were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were assessed using homeostasis model assessment (HOMA) based on fasting blood glucose (FBG) and fasting C-peptide index (FCP). Correlations and multiple linear regressions were implemented to determine the association of RDW and islet function indexes.. As the increase of serum RDW level, the presence of β-cell secretion increased(P < 0.05). Correlation analysis indicated that there were significant correlations between RDW and male sex, age, duration, TG, Cr, FCP, and HOMA-β in all subjects. Multiple linear regressions indicated that RDW was significantly correlated with HOMA-β in the total population in both unadjusted and adjusted analysis. This finding could be reproduced in the subgroup of low GAD titers for HOMA-β. RDW were significantly associated with HbA1c in LADA patients with high GAD titers, but the correlation was not found in subgroup with low GAD titers in either unadjusted analyses or adjusted analysis.. RDW is associated with β-cell function assessed by HOMA-β after adjusting for covariates in LADA patients with low GAD titers.

Topics: Adult; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Erythrocytes; Glucose Intolerance; Glycated Hemoglobin; Humans; Latent Autoimmune Diabetes in Adults; Male

We aimed to explore the performance of detrended fluctuation function (DFF) in distinguishing patients with latent autoimmune diabetes in adults (LADA) from type 2 diabetes mellitus (T2DM) with glucose data derived from continuous glucose monitoring.. In total, 71 LADA and 152 T2DM patients were enrolled. Correlations between glucose parameters including time in range (TIR), mean glucose, standard deviation (SD), mean amplitude of glucose excursions (MAGE), coefficient of variation (CV), DFF and fasting and 2-hour postprandial C-peptide (FCP, 2hCP) were analyzed and compared. Receiver operating characteristics curve (ROC) analysis and 10-fold cross-validation were employed to explore and validate the performance of DFF in diabetes classification respectively.. Patients with LADA had a higher mean glucose, lower TIR, greater SD, MAGE and CV than those of T2DM (. A more violent glucose fluctuation pattern was marked in patients with LADA than T2DM. We first proposed the possible role of DFF in distinguishing patients with LADA from T2DM in our study population, which may assist in diabetes classification.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Latent Autoimmune Diabetes in Adults

To investigate glycaemic variability (GV) patterns in patients with type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA).. A total of 842 subjects (510 T1D, 105 LADA, 227 T2D) were enrolled and underwent 1 week of continuous glucose monitoring (CGM). Clinical characteristics and CGM parameters were compared among T1D, LADA, and T2D. LADA patients were divided into two subgroups based on glutamic acid decarboxylase autoantibody titres (≥180 U/mL [LADA-1], <180 U/mL [LADA-2]) and compared. The C-peptide cut-offs for predicting a coefficient of variation (CV) of glucose ≥36% and a time in range (TIR) > 70% were determined using receiver operating characteristic analysis.. Twenty-seven patients (9 T1D, 18 T2D) were excluded due to insufficient CGM data. Sex, diabetes duration and HbA1c were comparable among the three groups. Fasting and 2-h postprandial C-peptide (FCP, 2hCP) increased sequentially across T1D, LADA, and T2D. T1D and LADA patients had comparable TIR and GV, whereas those with T2D had much higher TIR and lower GV (p < 0.001). The GV of LADA-1 was close to that of T1D, while the GV of LADA-2 was close to that of T2D. CP exhibited the strongest negative correlation with GV. The cut-offs of FCP/2hCP for predicting a CV ≥ 36% and TIR >70% were 121.6/243.1 and 128.9/252.8 pmol/L, respectively.. GV presented a continuous spectrum across T1D, LADA-1, LADA-2, and T2D. More frequent glucose monitoring is suggested for patients with impaired insulin secretion.. Chinese Clinical Trial Registration (ChiCTR) website approved by WHO; http://www.chictr.org.cn/ - ChiCTR2200065036.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Islets of Langerhans; Latent Autoimmune Diabetes in Adults

BACKGROUND We designed this study to develop and validate a prevalence model for latent autoimmune diabetes in adults (LADA) among people initially diagnosed with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS The study recruited 930 patients aged ≥18 years who were diagnosed with T2DM within the past year. Demographic information, medical history, and clinical biochemistry records were collected. Logistic regression was used to develop a regression model to distinguish LADA from T2DM. Predictors of LADA were identified in a subgroup of patients (n=632) by univariate logistic regression analysis. From this we developed a prediction model using multivariate logistic regression analysis and tested its sensitivity and specificity among the remaining patients (n=298). RESULTS Among 930 recruited patients, 880 had T2DM (96.4%) and 50 had LADA (5.4%). Compared to T2DM patients, LADA patients had fewer surviving b cells and reduced insulin production. We identified age, ketosis, history of tobacco smoking, 1-hour plasma glucose (1hPG-AUC), and 2-hour C-peptide (2hCP-AUC) as the main predictive factors for LADA (P<0.05). Based on this, we developed a multivariable logistic regression model: Y=-8.249-0.035(X1)+1.755(X2)+1.008(X3)+0.321(X4)-0.126(X5), where Y is diabetes status (0=T2DM, 1=LADA), X1 is age, X2 is ketosis (1=no, 2=yes), X3 is history of tobacco smoking (1=no, 2=yes), X4 is 1hPG-AUC, and X5 is 2hCP-AUC. The model has high sensitivity (78.57%) and selectivity (67.96%). CONCLUSIONS This model can be applied to people newly diagnosed with T2DM. When Y ≥0.0472, total autoantibody screening is recommended to assess LADA.

Topics: Adult; Age Factors; Aged; Blood Glucose; C-Peptide; China; Diabetes Mellitus, Type 2; Female; Humans; Ketosis; Latent Autoimmune Diabetes in Adults; Male; Middle Aged; Prevalence; Reproducibility of Results; Sensitivity and Specificity; Tobacco Smoking; Young Adult

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glutamate Decarboxylase; Humans; Latent Autoimmune Diabetes in Adults

In this study, we aimed to determine the frequency of and the clinical and metabolic features of patients with latent autoimmune diabetes in adults (LADA) at a single center in Turkey.. Patients over 30 years of age diagnosed with type 2 diabetes who did not require insulin for a minimum of 6 months following diagnosis were included. Data from 324 patients (163 women; 161 men), with a mean age of 54.97 ± 7.53 years, were analyzed in the study. Levels of antibodies to glutamate decarboxylase (anti-GAD) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies.. We observed a LADA frequency of 1.5% among Turkish patients followed for type 2 diabetes. The presence of obesity and metabolic syndrome did not exclude LADA, and patients with LADA had worse glycemic control than patients with type 2 diabetes did.

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Infant; Latent Autoimmune Diabetes in Adults; Male; Middle Aged; Turkey

To search for risk factors that could predict progression in latent autoimmune diabetes in adults (LADA) and compare them with those for type 2 diabetes.. This study included 175 participants with LADA (autoantibody positive, without insulin treatment ≥1 year after diagnosis) and 2331 participants with type 2 diabetes (autoantibody negative, without insulin treatment ≥1 year after diagnosis) from the HUNT2 and HUNT3 surveys. We used Cox regression models and receiver operating characteristic curve analysis to identify predictive factors for progression to insulin dependency within 10 years.. Low C-peptide levels (<0.3 nmol/L) predicted progression to insulin dependency within 10 years in both LADA (hazard ratio [HR] 6.40 [95% CI, 2.02-20.3]) and type 2 diabetes (HR 5.01 [95% CI, 3.53-7.10]). In addition, a high glutamic acid decarboxylase autoantibody (GADA) level (HR 5.37 [95% CI, 1.17-24.6]) predicted progression in LADA. Together, these two factors had a discriminatory power between non-progressors and progressors of area under the curve (AUC) of 0.86 (95% CI, 0.80-0.93). In type 2 diabetes, younger age at diagnosis (<50 years: HR 2.83 [95% CI, 1.56-5.15]; 50-69 years: HR 2.11 [95% CI, 1.19-3.74]), high HbA1c levels (≥53 mmol/mol, HR 2.44 [95% CI, 1.72-3.46]), central obesity (HR 1.65 [95% CI, 1.06-2.55]) and a body mass index of more than 30 kg/m. Factors predicting progression to insulin dependence are partly similar and partly dissimilar between LADA and type 2 diabetes. A constellation of low C-peptide and high GADA levels identifies LADA patients who are probable to progress to insulin dependence.

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 2; Glutamate Decarboxylase; Humans; Insulin; Latent Autoimmune Diabetes in Adults

The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diagnosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electrochemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely.. Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 diabetes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarboxylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared.. Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Compared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (. Patients with ECL-GAD65 antibody-negative share a similar phenotype with type 2 diabetes mellitus patients, whereas patients with ECL-GAD65 antibody-positive resemble those with type 1 diabetes mellitus. Thus, the detection of GADA using ECL may help to identify the subtype of LADA.

Topics: Adolescent; Adult; Autoantibodies; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Islets of Langerhans; Latent Autoimmune Diabetes in Adults; Male; Middle Aged; Phenotype; Young Adult

To explore the decline pattern and possible determinants of beta-cell function progression in patients with latent-onset autoimmune diabetes in adults (LADA).. In this 8-year prospective study, 106 LADA individuals underwent annual follow-up and their pattern of beta-cell function progression was assessed. Beta-cell function failure was defined by fasting C-peptide (FCP) < 75 pmol/L. Other clinical characteristics, including age of onset, body mass index (BMI), and glutamic acid decarboxylase autoantibody (GADA) titer, were analyzed to find out possible determinants of beta-cell function progression.. The dropout rate was 4.7%. During the 8-year follow-up period, 29 (28.7%) of the 101 subjects developed beta-cell function failure. The decline pattern of C-peptide in LADA was biphasic, showing an initial rapid linear progression and then followed by a stable mode. The declination speed of FCP was 55.19 pmol/L/year (95% CI, -62.54 to -47.84, P < 0.001) during the first 5 years and 4.62 pmol/L/year (95% CI, -69.83 to 60.60, P = 0.790) thereafter. Further analysis showed that GADA titer was the most valuable discriminatory parameter related to a higher risk of development of beta-cell function failure (GADA titer of 173.5 WHO units/mL; area under the curve [AUC], 0.824). Beta-cell function failure occurred in 71.3% of high-GADA titer patients while only 6.2% of low-titer patients.. The decline pattern of C-peptide was a fast-followed-by-slow biphasic mode, with about a quarter of LADA patients developing beta-cell function failure during the first 8 years. GADA titer less than 173.5 WHO units /mL was propitious for the preservation of beta-cell function.

Topics: Adult; Age of Onset; Autoantibodies; Body Mass Index; C-Peptide; Female; Glutamate Decarboxylase; Humans; Insulin-Secreting Cells; Islets of Langerhans; Latent Autoimmune Diabetes in Adults; Male; Middle Aged; Prospective Studies

To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications.. Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed.. Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications.

Topics: Adult; Age of Onset; Autoantibodies; Autoantigens; Blood Glucose; Blood Pressure; C-Peptide; Cross-Sectional Studies; Diabetes Complications; Female; Glutamate Decarboxylase; Humans; Insulin; Latent Autoimmune Diabetes in Adults; Lipids; Male; Middle Aged; Overweight; Retrospective Studies; Spain

Latent autoimmune diabetes in adults (LADA) usually refers to GAD65 autoantibodies (GADAb)-positive diabetes with onset after 35 years of age and no insulin treatment within the first 6 months after diagnosis. However, it is not always easy to distinguish LADA from type 1 or type 2 diabetes. In this study, we examined whether metabolite profiling could help to distinguish LADA (

Topics: Adult; Age of Onset; Autoantibodies; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Female; Gas Chromatography-Mass Spectrometry; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Latent Autoimmune Diabetes in Adults; Male; Metabolome; Middle Aged; Principal Component Analysis; Sweden; Young Adult