Pancreatic beta-cell function dynamics in youth with GCK, HNF1A, and KCNJ11 genes mutations during mixed meal tolerance test

Objective: The aims were (1) to assess beta-cell function in GCK diabetes patients over 2-year period; (2) to evaluate the dynamics of beta-cell function in HNF1A and KCNJ11 patients after treatment optimization; using mixed meal tolerance test (MMTT) as a gold standard for non-invasive beta-cell function assessment. Research design and methods: Twenty-two GCK diabetes patients, 22 healthy subjects, 4 patients with HNF1A and 2 with KCNJ11 were recruited. Firstly, beta-cell function was compared between GCK patients versus controls; the dynamics of beta-cell function were assessed in GCK patients with two MMTTs in 2-year period. Secondly, the change of beta-cell function was evaluated in HNF1A and KCNJ11 patients after successful treatment optimization in 2-year period. Results: GCK diabetes patients had lower area under the curve (AUC) of C-peptide (CP), average CP and peak CP compared to controls. Also, higher levels of fasting, average, peak and AUC of glycemia during MMTT were found in GCK patients compared to healthy controls. No significant changes in either CP or glycemia dynamics were observed in GCK diabetes group comparing 1st and 2nd MMTTs. Patients with HNF1A and KCNJ11 diabetes had significantly improved diabetes control 2 years after the treatment was optimized (HbA1c 7.1% vs. 5.9% [54 mmol/mol vs. 41 mmol/mol], respectively, p = 0.028). Higher peak CP and lower HbA1c were found during 2nd MMTT in patients with targeted treatment compared to the 1st MMTT before the treatment change. Conclusion: In short-term perspective, GCK diabetes group revealed no deterioration of beta-cell function. Individualized treatment in monogenic diabetes showed improved beta-cell function.</p

Serum Cystatin C as a Biomarker for Early Diabetic Kidney Disease and Dyslipidemia in Young Type 1 Diabetes Patients

Background and objectives: This study aimed to assess the clinical significance of serum cystatin C in the early diagnosis of renal injury and its association with dyslipidemia in young T1D patients. Materials and Methods: A total of 779 subjects were evaluated for kidney function by estimating glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) and cystatin C (eGFRcys). Results: The median age of study subjects was 16.2 years (2.1;26.4), diabetes duration&mdash;5.3 years (0.51;24.0). The median of HbA1c was 8% (5.2;19.9) (64 mmol/mol (33.3;194)); 24.2% of participants had HbA1c &lt; 7% (53 mmol/mol). Elevated albumin excretion rate was found in 13.5% of subjects. The median of cystatin C was 0.8 mg/L (0.33;1.71), the median of creatinine&mdash;63 &micro;mol/L (6;126). The median of eGFRcys was lower than eGFRcreat (92 mL/min/1.73 m2 vs. 101 mL/min/1.73 m2, p &lt; 0.001). A total of 30.2% of all patients were classified as having worse kidney function when using cystatin C vs. creatinine for eGFR calculation. Linear correlations were found between cystatin C and HbA1c, r = &minus;0.088, p &lt; 0.05, as well as cystatin C and HDL, r = &minus;0.097, p &lt; 0.01. Conclusions: This study showed that cystatin C might be used as an additional biomarker of early kidney injury in young patients with T1D

Kinetics of C-peptide during mixed meal test and its value for treatment optimization in monogenic diabetes patients

Aim: The mixed meal tolerance test (MMTT) is a gold standard for evaluating beta-cell function. There is limited data on MMTT in monogenic diabetes (MD). Therefore, we aimed to analyze plasma C-peptide (CP) kinetics during MMTT in young MODY and neonatal diabetes patients as a biomarker for beta-cell function. Methods: We included 41 patients with MD diagnosis (22 GCK, 8 HNF1A, 3 HNF4A, 4 KCNJ11, 2 ABCC8, 1 INS, 1 KLF11). Standardized 3-hour MMTT with glycemia and plasma CP measurements were performed for all individuals. Pancreatic beta-cell response was assessed by the area under the curve CP (AUCCP), the baseline CP (CPBase) and the peak CP (CPmax). Threshold points of CPBase, CP90, CPmaxand CPAUCwere determined from analysis of ROC curves. Results: GCK diabetes patients had significantly higher AUCCP, CPBaseand CPmaxcompared to HNF4A and KCNJ11 patients. In HNF4A, KCNJ11 and ABCC8 patients with all CP levels &lt; 200 pmol/L, the treatment change attempt to sulfonylurea agent was unsuccessful. The ROC analysis showed that CP baseline threshold equal or higher to 133.5 pmol/L could be used to predict successful switch to oral agents. Conclusion: A pretreatment challenge with MMTT might be used to guide the optimal treatment after molecular diagnosis of MD.</p

Factors Affecting Cardiovascular Risk in Children, Adolescents, and Young Adults with Type 1 Diabetes

Cardiovascular risk and obesity are becoming major health issues among individuals with type 1 diabetes (T1D). The aim of this study was to evaluate cardiovascular risk factors and obesity in youth with T1D in Lithuania. Methods. 883 patients under 25 years of age with T1D for at least 6 months were investigated. Anthropometric parameters, blood pressure, and microvascular complications were evaluated, and the lipid profile and HbA1c were determined for all patients. Results. Study subjects’ mean HbA1c was 8.5±2%; 19.5% were overweight and 3.6% obese. Hypertension and dyslipidemia were diagnosed in 29.8% and 62.6% of participants, respectively. HbA1c concentration was directly related to levels of total cholesterol (r=0.274, p<0.001), LDL (r=0.271, p<0.001), and triglycerides (r=0.407, p<0.001) and inversely associated with levels of HDL (r=0.117, p=0.001). Prevalence of dyslipidemia increased with duration of diabetes (p<0.05). Hypertension was more prevalent in overweight and obese compared to normal-weight patients (40.6 and 65.6 vs. 25.6%, respectively, p<0.001). Frequency of microvascular complications was higher among patients with dyslipidemia (27.2 vs. 18.8%, p=0.005) and among those with hypertension (25.9 vs. 23.2%, p<0.001). Conclusion. The frequency of cardiovascular risk factors is high in youth with T1D and associated with diabetes duration, obesity, and metabolic control

The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter?

Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes. The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0-25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies

The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter?

Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes. The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0-25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo