Switching from Multiple Insulin Injections to a Fixed Combination of Degludec and Liraglutide in Patients with Type 2 Diabetes Mellitus: Results from the Simplify Study After 6 Months.

INTRODUCTION: This study aimed to evaluate the effectiveness and safety of switching from basal bolus insulin treatment (BBIT) to a fixed combination of insulin degludec and liraglutide (IDegLira) in patients with type 2 diabetes mellitus (T2DM) who had preserved insulin secretion but inadequate glucose control. The study also aimed to assess the feasibility of implementing this therapeutic approach in common clinical practice settings. METHODS: This was a non-randomized, open-label, multicenter, prospective, single-arm study involving 234 patients with T2DM who were receiving BBIT. Inclusion criteria were duration of diabetes mellitus > 60 months, stable total daily dose of insulin (TDDI) ranging from > 20 to < 70 IU/day (approx. > 0.3 to < 0.7 IU/kg body weight/day), C-peptide levels > 10% above the lower limit, HbA1c levels > 7% and < 10% (Diabetes Control and Complications Trial), and body mass index > 25 kg/m2. The primary endpoints were changes in glycated hemoglobin (HbA1c) and body weight at week 28 after treatment switching. Secondary endpoints included changes in the 7-point glycemic profile, hypoglycemia frequency, blood pressure, blood lipids, liver enzymes, insulin dose, and a patient questionnaire focusing on treatment satisfaction, concerns and impact on daily activities. A subgroup of 55 patients underwent continuous glucose monitoring (CGM) with the evaluation of CGM-derived parameters, such as time in range (TIR), time above range (TAR), time below range (TBR), hypoglycemia, and glucose variability. RESULTS: A significant decrease in HbA1c (8.6% vs. 7.6%; p < 0.0001) and body weight (97.8 vs. 94.0 kg; p < 0.0001) was observed at week 28 after treatment switching. Significant improvements were also seen in all measurements of the 7-point glycemic profile (p < 0.0001), reduction in the number of hypoglycemia episodes per patient, and the proportion of patients with at least one hypoglycemia event (p < 0.001). Furthermore, there was a significant decrease in daily insulin dose (55.6 vs. 32.7 IU/day; p < 0.0001), as well as improvements in blood pressure, blood lipids, and liver enzymes (gamma glutamyl transferase and alanine aminotransferase). The subgroup of patients who underwent CGM showed a significant increase in TIR (57.9% vs. 69.0%; p < 0.01) and a decrease in TAR (40.1% vs. 28.8%; p < 0.01), while TBR, hypoglycemia (number of episodes per patient and proportion of patients), and glucose variability did not change significantly. CONCLUSION: The results of this study suggest that switching from BBIT to IDegLira in patients with T2DM and preserved insulin secretion can simplify treatment without compromising glycemic control. The switch to IDegLira was associated with significant improvements in various glucose control parameters, including HbA1c, glycemic profile, hypoglycemia, insulin doses, and CGM-derived parameters TIR and TAR. Additionally, it led to significant reductions in body weight, blood pressure, lipid profile, and liver enzyme levels. Switching to IDegLira may be considered a safe and beneficial approach in clinical practice settings, offering metabolic and individual advantages.

The effect of alfacalcidiol and metformin on metabolic disturbances in women with polycystic ovary syndrome.

BACKGROUND: The aim of this randomized clinical trial (RCT) was to evaluate the effect of vitamin D supplementation in obese, insulin-resistant (IR) and vitamin D-deficient polycystic ovary syndrome (PCOS) women on metabolic abnormalities in comparison to the effect of metformin or combined metformin plus vitamin D therapy. MATERIAL AND METHODS: Thirty-nine PCOS women who fulfilled the inclusion criteria were randomized into three groups and treated with alfacalcidiol, combined alfacalcidiol and metformin therapy and metformin for 6 months. Body weight, body mass index (BMI), waist circumference, total body fat and fat distribution were measured before and after 6 months of treatment. Plasma fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and lipid profiles were measured at the same time. RESULTS: There was a significant decrease in body weight, BMI, waist circumference, total body fat and serum glucose levels in the metformin group (p<0.05), whereas PCOS women treated with alfacalcidiol did not significantly change their anthropometric and metabolic parameters. A significant decrease in waist circumference (p<0.05) in the group treated with metformin and alfacalcidiol was detected without other significant metabolic changes (all p>0.05). There were no significant changes in metabolic parameters (p>0.05) after vitamin D therapy except for a slight but non-significant trend towards higher high-density lipoprotein (HDL) cholesterol levels (p=0.087). CONCLUSION: We conclude that vitamin D supplementation has no significant effect on anthropometric and metabolic parameters in PCOS women. Metformin has been still the most effective modality for the treatment of metabolic changes in PCOS.

[Vitamin D and Polycystic Ovary Syndrome]. / Vitamín D a syndróm polycystických ovárií.

Currently there is growing evidence on possible influence of vitamin D (VD) on reproductive function in both females and males. The relationship between VD and clinical or laboratory manifestations of polycystic ovary syndrome (PCOS) seems to be mostly evaluated. Patients with PCOS have been demonstrated to have significantly lower levels of serum VD and they also have the higher prevalence of vitamin D deficiency as compared to controls. Some studies documented the relation of VD to serum androgen levels, other found that VD correlated with metabolic parameters (body weight, insulin resistance and lipid profile) only. Several interventional studies demonstrated that VD replacement improved these metabolic parameters in PCOS women with VD deficiency. On the other hand some studies also documented improvement of ovarian function and androgen levels. Also vitamin D replacement may represent an additional treatment in VD deficient PCOS women with the aim to improve phenotypic manifestations. It requires further randomized interventional studies on larger groups of patients.Key words: metabolic syndrome - polycystic ovary syndrome - vitamin D.

[Clinical implications of polycystic ovary syndrome]. / Klinické dôsledky syndrómu polycystických ovárií.

UNLABELLED: Polycystic ovary syndrome (PCOS) is a heterogeneous and complex endocrine disease which among the female population belongs to the most widespread endocrinopathies and it is the most frequent cause of hyperthyroidism, anticoagulation and infertility. Insulin resistance is one of the important diabetology factors impacting hyperglycaemia in a majority of women with PCOS (60-80 %). Clinical expressions of PCOS include reproduction disorders, metabolic characteristics and psychological implications. Reproduction disorders include hyperthyroidism, menstruation cycle disorders, infertility and pregnancy complications as well as early abortions, gestational diabetes and pregnancy induced hypertension. Long-term metabolic risks of PCOS include type 2 diabetes mellitus, dyslipidemia, arterial hypertension and endothelial dysfunction. The available data confirms higher incidence of cardiovascular diseases in women with PCOS. In particular among obese women PCOS is more frequently associated with non-alcoholic hepatic steatosis, sleep apnoea syndrome and endometrial cancer. The literature includes some controversial data about the relationship between PCOS and autoimmunity. Women with PCOS are more prone to suffer from insufficient confidence with higher incidence of anxiety, depression, bipolar disorder and eating disorders. KEY WORDS: autoimmunity - diabetes mellitus - pregnancy - insulin resistance - metabolic syndrome - menstrual disorders - polycystic ovary syndrome.

Prevalence of vitamin D deficiency in Slovak women with polycystic ovary syndrome and its relation to metabolic and reproductive abnormalities.

OBJECTIVE: To investigate prevalence of vitamin D deficiency and its relation to clinical, anthropometrical, and biochemical findings in polycystic ovary syndrome (PCOS) and controls. DESIGN: Case-control prospective observational study. SETTINGS: Department of Internal medicine, L.P. University hospital. PATIENT(S): 99 PCOS women and 66 controls. MAIN OUTCOME MEASURE(S): 25-hydroxyvitamin D level (25(OH)D), anthropometric, endocrine, and metabolic parameters in both groups. RESULTS: There was no significant difference in 25(OH)D levels between PCOS women and controls (24.79 ± 10.77 vs 25.07 ± 10.14 ng/ml, p = 0.868) and also in the prevalence of 25(OH)D deficiency in both groups (80 vs 70 %; p = 0.138). Vitamin D-deficient PCOS patients had significantly higher body mass index (BMI), fasting insulin, and homeostasis model assessment-insulin resistance (median [quartiles]: 2.24 [1.38; 3.51] vs 1.23 [0.79; 1.66]; p< 0.05, age-and BMI-adjusted p = 0.036) and borderline higher glycemia (4.7 ± 0.5 vs 4.5 ± 0.4 mmol/l; p = 0.05; p_adj = 0.95) compared with vitamin D-deficient controls. PCOS women with metabolic syndrome (MS) had lower serum 25(OH)D compared with those without MS (20.6 ± 8.3 vs 25.9 ± 11.3 ng/ml, p = 0.049). 25(OH)D correlated positively with high-density lipoprotein cholesterol in all subjects (r = 0.159, p = 0.043) and negatively with luteinizing hormone/follicle-stimulating hormone ratio (r = - 0.211, p = 0.037). CONCLUSION: Insulin resistance and other metabolic abnormalities in PCOS women seem to be related to PCOS rather than to vitamin D deficiency.

The prevalence of non organ specific and thyroid autoimmunity in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is commonly associated with endocrine, metabolic, cardiovascular and other morbidities. However its association with autoimmune diseases is still controversial. AIM: The aim of this study was to assess the prevalence of non organ-specific and antithyroid, antibodies in PCOS women compared to healthy controls. METHODS: The study included 152 women with PCOS and 76 healthy controls for the evaluation of non organ-specific autoimmunity and 64 PCOS and 68 controls for the study of organ-specific autoimmunity. All sera were tested for autoantibodies.using the ELISA method. RESULTS: There were no significant differences in the prevalence of ANA, SSA, SSB, anti-dsDNA, anti-RNP, ANCA/MPO or ANCA/PR3 between PCOS and controls. The prevalence of ACLA IgG was higher in controls than PCOS (5.4% v.s. 0%, P=0.011). Patients had a higher prevalence of anti-TPO antibodies (18.75% v.s. 7.35%, P=0.045) and slightly but not significantly higher prevalence of autoimmune thyroiditis (18.75% v.s. 10.29%) than controls. CONCLUSION: The prevalence of non organ-specific autoantibodies in PCOS women is low and similar to controls. On the other hand, we found a slightly higher prevalence of thyroid autoimmunity in PCOS women.

Clinically silent adrenal adenomas - their relation to the metabolic syndrome and to GNB3 C825T gene polymorphism.

OBJECTIVES: Aim of the study was to assess the prevalence of C825T GNB3 gene polymorphism in patients with adrenal incidentaloma (AI) as well as its relation to the metabolic syndrome (MS) and cortisol status. SUBJECT AND METHODS: Alltogether 82 subjects (50 patients with AI, mean age 57.9 + 15 years and 32 subjects without AI, mean age 53.8 + 6.9 years) were included in this study. Parameters of glucose and lipid metabolism, serum adiponectin and the single nucleotide polymorphism C825T in GNB3 gene using PCR-RFLP method were examined. To detect subclinical Cushing syndrome an overnight dexamethason test was performed in all patients with AI. RESULTS: Patients with AI had signifcantly higher BMI, HOMA, triacylglycerols (p < 0.05) and significantly lower serum adiponectine (p < 0.05) than controls. There were no significant differences in metabolic parameters between group with and without subclinical Cushing syndrome (SCS). The prevalence of T allele of GNB3 gene in patients with AI was not significantly higher as compared with control group (32% vs. 47%). No significant differences in serum glucose and lipids between carriers of T and C alleles were detected. However carriers of T allele had significantly lower serum adiponectin than those with allele C (p < 0.01). CONCLUSION: We conclude that patients with AI had significantly higher cardiovascular risk factors that is not related to the presence of SCS. Moreover patients with AI and TC or TT genotype have significantly lower serum adiponectin which may be an early symptom of metabolic syndrome in patients with AI.

The prevalence of Gly972Arg and C825T polymorphisms in Slovak women with polycystic ovary syndrome and their relation to the metabolic syndrome.

AIM: To assess the prevalence of IRS-1 Gly972Arg and GNB3 C825T polymorphisms in women with polycystic ovary syndrome (PCOS) and their relation to the metabolic syndrome and hyperandrogenaemia. METHODS: Fifty-three female patients with diagnosis of PCOS and 21 healthy women were genotyped for the commom Gly972Arg and C825T polymorphisms. Body mass index, serum glucose, insulin, insulin sensitivity index HOMA (homeostasis model assessment) and serum lipoproteins were estimated. RESULTS: The prevalence of Gly972Arg genotype in PCOS women was 22.64% and was not significantly higher than in control group with the prevalence 9.52%. The frequency of T alleles was 28% in PCOS group that was similar to control group (29%). We did not find the significant differences in the frequency of TC + TT genotypes between patients and controls. There were no significant differences in serum glucose, insulin, lipoproteins, index HOMA, as well as BMI and waist circumference between patients with GlyArg and GlyGly. Both CC and TC/TT genotype patients had similar values of BMI, waist and measured biochemical variables. Moreover, Gly972Arg and C825T polymorphisms were not related to hormonal status of PCOS women. CONCLUSION: The Gly972Arg and C825T polymorphisms are associated neither with PCOS nor with metabolic syndrome in the Slovak female population.