Primary hyperparathyroidism in young patients is associated with metabolic disorders: a prospective comparative study.

BACKGROUND: Components of metabolic syndrome can be observed in patients with primary hyperparathyroidism (PHPT). The link between these disorders remains unclear due to the lack of relevant experimental models and the heterogeneity of examined groups. The effect of surgery on metabolic abnormalities is also controversial. We conducted a comprehensive assessment of metabolic parameters in young patients with PHPT. METHODS: One-center prospective comparative study was carried out. The participants underwent a complex biochemical and hormonal examination, a hyperinsulinemic euglycemic and hyperglycemic clamps, a bioelectrical impedance analysis of the body composition before and 13 months after parathyroidectomy compared to sex-, age- and body mass index matched healthy volunteers. RESULTS: 45.8% of patients (n = 24) had excessive visceral fat. Insulin resistance was detected in 54.2% of cases. PHPT patients had higher serum triglycerides, lower M-value and higher C-peptide and insulin levels in both phases of insulin secretion compared to the control group (p < 0.05 for all parameters). There were tendencies to decreased fasting glucose (p = 0.031), uric acid (p = 0.044) and insulin levels of the second secretion phase (p = 0.039) after surgery, but no statistically significant changes of lipid profile and M-value as well as body composition were revealed. We obtained negative correlations between percent body fat and osteocalcin and magnesium levels in patients before surgery. CONCLUSION: PHPT is associated with insulin resistance that is the main risk factor of serious metabolic disorders. Surgery may potentially improve carbohydrate and purine metabolism.

Clinical Pharmacology of Insulin Aspart Biosimilar GP40071: Pharmacokinetic/Pharmacodynamic Comparability in Hyperinsulinemic Euglycemic Clamp Procedure.

Insulin aspart is a short-acting insulin analogue that is used to control postprandial glycemia levels in diabetic patients. The aim of this clinical trial was to compare the pharmacokinetics and pharmacodynamics of GP40071 (GP-Asp) and NovoRapid Penfill (Novo-Asp) in a hyperinsulinemic euglycemic clamp (HEC). This trial was conducted as a part of a GP40071 biosimilar clinical development program. This was a phase I randomized, double-blind, two-period crossover study. Twenty-six healthy male volunteers aged 18 to 45 years who met the inclusion criteria underwent the procedure of an HEC following a single subcutaneous injection of 0.3 IU/kg of either GP-Asp or Novo-Asp into the abdomen. After doses, plasma glucose levels were monitored every 5 minutes for 8 hours. The adjustment of the glucose infusion rate (GIR) was based on the blood glucose measurements. The GIR values were used to evaluate the PD profiles of the studied drugs. Regular blood sampling was performed during the study to obtain sufficient pharmacokinetic data. The 90% confidence intervals for the geometric mean ratios of the pharmacokinetic (AUCins.0-t , Cins.max ) and pharmacodynamic (GIRmax , AUCGIR0-t ) parameters of GP-Asp were within the 80%-125% comparability limits. The safety profiles of the drugs were also comparable. Bioequivalence, similar PD, and safety of GP-Asp and Novo-Asp were demonstrated.

The efficacy and safety of GP40081 (insulin aspart biphasic 30) compared with NovoMix® 30 in Type 2 diabetes patients.

Aim: To evaluate the safety and efficacy of insulin Aspart-Mix biosimilar candidate GP40081 (GP-Asp30) compared with NovoMix® 30 (NN-Asp30). Materials & methods: In a randomized open-label, active-controlled, 26-week non-inferiority clinical trial 264 patients with Type 2 diabetes mellitus were randomized 1:1 to receive once-daily GP-Asp30 or NN-Asp30. The primary safety end point was the immune response rate. Efficacy outcomes were a mean change in HbA1c (primary), frequency of achieving a glycemic g fasting plasma glucose levels, 7-point glucose profiles, and insulin doses. Results: The immune response developed in 10/126 (8%) participants in the GP-Asp30 group and in 10/125 (8%) participants in the NN-Asp30 group (p = 1.000). The mean difference in HbA1c change between groups was 0.12 (95%CI [-0.14, 0.38]). Other secondary efficacy and safety outcomes weren't statistically different between the two groups. Conclusion: GP-Asp30 demonstrated similar safety and efficacy compared with NN-Asp30 and may be considered a biosimilar insulin.

Identifying the unmet needs of individuals with Type 2 diabetes: an international web-based survey.

Aim: To identify and understand the main unmet needs of individuals with Type 2 diabetes (T2D). Materials & methods: An online survey was conducted in Brazil, China and Russia of individuals with recently diagnosed T2D. Results: The survey, involving 300 individuals with T2D, identified a need for more information regarding food/diet and for increased awareness of T2D symptoms. While most participants (94%) had experienced symptoms prior to their diagnosis, only 55% of symptomatic individuals sought medical attention. Conclusion: Novel strategies to increase awareness of diabetes should be developed and tested, and may enable earlier diagnosis and improve patients' quality of life.

Lay abstract Type 2 diabetes (T2D) negatively impacts an individual's health-related quality of life and represents a significant burden of disease worldwide. Although previous studies have examined the unmet needs of patients with diabetes, no recent studies have evaluated the needs of individuals with T2D in Brazil, China or Russia. This study used an online questionnaire to identify and understand the main unmet needs of individuals who had been recently diagnosed with T2D from these countries. Several potential needs were identified, including the need for more information and support about food and diet, a new noninvasive solution for blood glucose monitoring and increased awareness of T2D symptoms. Our study also identified possible innovative solution to address these needs.

Safety and efficacy of GP40071 compared with originator insulin aspart (NovoRapid® Penfill®) in Type 1 diabetes mellitus.

Aim: To compare safety and efficacy of GP40071 insulin aspart (GP-Asp) and NovoRapid® (NN-Asp). Materials & methods: This randomized open-label, active-controlled, 26-week non-inferiority Phase III clinical trial enrolled 264 Type 1 diabetes mellitus patients (HbA1c: 7.1-12.0%) randomized 1:1 to once daily GP-Asp (n = 132) or NN-Asp (n = 132). The primary safety end point was immune response at week 26. Results: The groups were similar in frequency of immune response (p = 0.323) and in other safety end points. Mean HbA1c change from baseline was -0.57% for GP-Asp and -0.56% for NN-Asp and did not differ between groups (p = 0.955). Intergroup mean difference of HbA1c level change (95% CI) at week 26 from baseline was 0.00 (-0.26, 0.25) %. Insulin doses, fasting plasma glucose levels and seven-point glucose profiles were similar between groups (p > 0.05). The number of patients experiencing hypoglycemic episodes did not differ between the groups (p = 0.497). Conclusion: GP-Asp demonstrated similar safety and efficacy. Trial registration number: NCT04079413 (ClinicalTrials.gov).

Safety and efficacy of GP40061 compared with originator insulin glargine (Lantus®): a randomized open-label clinical trial.

Aim: To compare safety (immunogenicity) and efficacy of GP40061 insulin glargine (GP-Gla) and Lantus® (Sanofi glargine, Sa-Gla) in people with diabetes mellitus. Materials & methods: This randomized open-label, 26-week clinical trial enrolled 180 Type 1 diabetes mellitus patients (HbA1c 6.5-12.0%), randomized 1:1 to once daily GP-Gla (n = 90) or Sa-Gla (n = 90). The primary end point was immune response at 26th week. Results: The frequency of immune response was similar in GP-Gla and Sa-Gla (p = 1.000). Groups were similar in terms of other safety end points. Mean HbA1c change from baseline was -0.66% for GP-Gla and -0.77% for Sa-Gla, and did not differ between groups (p = 0.326). Insulin doses, fasting plasma glucose and seven-point glucose profiles were similar between groups. Conclusion: GP-Gla and Sa-Gla demonstrated similar safety and efficacy. ClinicalTrials.gov Identifier: NCT04022993.

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population.

BACKGROUND: The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. METHODS: The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-ß were used to measure insulin resistance and ß-cell secretory function, respectively. RESULTS: The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired ß-cell function. CONCLUSION: In the Russian population, genes, which affect insulin synthesis and secretion in the ß-cells of the pancreas, play a central role in the development of T2DM.