Once-weekly semaglutide use in glucagon-like peptide-1 receptor agonist naïve patients with type 2 diabetes in North Macedonia: Real-world data from the MIRAGE study.

AIMS: The MIRAGE study aimed to evaluate the real-world use of once weekly (OW) subcutaneous semaglutide in glucagon-like peptide-1 receptor agonist naïve type 2 diabetes patients in routine clinical practice in North Macedonia. METHODS: MIRAGE was a multicentre, single-arm, retrospective and 30-weeks study, conducted in North Macedonia. Primary [change in glycated haemoglobin (HbA1c)] and secondary endpoints [change in body weight, fasting plasma glucose (FPG), lipid parameters, blood pressure, waist circumference, glycaemic and weight-loss target achievement] were evaluated between baseline and end of study (EOS). RESULTS: Baseline characteristics of 314 patients enrolled in the study were, mean age: 55.5 years, HbA1c: 9.0 %, diabetes duration: 7.8 years, body weight: 105.2 kg and waist circumference: 114 cm. Patients at EOS experienced statistically significant estimated mean change in HbA1c: -2.2 % points, body weight: -9.0 kg, and FPG: -4.1 mmol/L (all p < 0.0001). At EOS, 62.1 % patients achieved HbA1c < 7 %, and 79.3 % had ≥ 1 % HbA1c reduction. A weight reduction of ≥ 3 % and ≥ 5 % was noted in 88.3 % and 73.3 % patients, respectively. No new safety concern has emerged. CONCLUSIONS: Findings from MIRAGE study demonstrated glycaemic and weight-loss benefits of semaglutide, with improvements in other cardiometabolic parameters. The study supports real-world OW subcutaneous semaglutide use in North Macedonia.

Assessment of Prevalence and Risk Factors for Diabetic Retinopathy in Patients with Type 1 and Type 2 Diabetes Examined at a Tertiary Care.

Introduction: Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and the leading cause of visual impairment and blindness. The aim of the study was to estimate and compare the prevalence of DR and to determine an association between DR and systemic risk factors in hospitalized type 1 (DMT1) and type 2 (DMT2) diabetic patients. Material and methods: We analyzed 260 patients with diabetes, 43 with DMT1 and 217 with DMT2. The following data were collected: age, gender, type and duration of diabetes, glycemic control, blood pressure, estimated glomerular filtration rate, ophthalmologic examinations and routine biochemical parameters. Results: Out of the total number of 260 patients, 77 (29.6%) had non-proliferative DR (NPDR), 21 (8.1%) had proliferative DR (PDR), 29 (11.1%) had diabetic macular edema (DME), and 69 (23.5%) had diabetic cataracts. Forty-three (16.5%) patients were previously diagnosed with DMT1 and 217 (83.5%) with DMT2. The duration of diabetes was not significantly longer in DMT1 (12.8±11.2 years) in comparison to DMT2 (11.07±8.1 years). The prevalence of NPDR and PDR did not differ statistically in either groups. DME was more prevalent in DMT2 than in DMT1 (P<0.05). Diabetic cataract was found in 26.7% vs. 6.7% of patients with DMT2 and DMT1, respectively (p<0.01). The duration of diabetes significantly correlated with NPDR and PDR in DMT1 (r=o.31, p<0.05; r=0.55, p<0.001, respectively). In DMT2, significant correlations were found between the duration of diabetes and cataract, NPDR, PDR and DME (r=0.31, p<0.001; r=0.43 p<0.01, r=0.16 p<0.05 and r=0.20 p<0.01, respectively). Fasting plasma glucose (FPG) significantly correlated with PDR (r=0.258, p<0.05), while HbA1c with DME (r= 0.15 p<0.05). Conclusion: The duration of diabetes and hyperglycemia were associated with DR in both types of diabetes.

Alström Syndrome with Early Vision and Hearing Impairement.

Alström syndrome (ALMS) is an autosomal recessive disorder characterized by multiple organ involvement, including progressive cone-rod dystrophy, sensorineural hearing loss, childhood obesity, and type 2 diabetes mellitus. Pathogenic variants in the ALMS1 gene are the known cause for the occurrence of this devastating condition. Here we report on a 12 year old boy referred to the University Clinic with early signs of impaired hearing and vision, obesity, and scoliosis. Central vision was first affected, followed by peripheral vision. In addition, his weight began increasing after the age of two years, reaching 78 kg at a height of 157 cm (BMI 31.64). No polydactyly was present. His mental development was normal in spite of his hearing and vision impairments. There was acanthosis nigricans on the neck. ECG and the cardiac ultrasound were normal. At the age of 12 years, his testicles are 12 ml and his pubertal status is P2 A2. OGTT revealed impaired glucose tolerance with elevated insulin concentrations 121ulU/mL (reference range 2,00-29,1 ulU/mL). Renal function was unaffected, liver functions were normal. Uric acid and lipids were within normal plasma concentrations. A Whole Exome Sequencing was performed and a homozygous ALMS1 pathogenic, frameshift gene variant (LRG_741t1(ALMS1):c.4156dup; p.Thr1386AsnfsTer15) was determined as the cause of the disease. Both parents were carriers for the variant. The absence of mental retardation and polydactyly differentiates Alström and Bardet-Biedle syndrome.

Indexes of Insulin Resistance in Hyperinsulinemic Polycystic Ovary Syndrome in a Macedonian Cohort of Women of Reproductive Age: A Cross-Sectional Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is complex hormonal, metabolic and reproductive disorder and is a leading cause of female infertility. Hyperinsulinemia secondary to insulin resistance plays important role in the pathogenesis of PCOS. AIM: To assess the sensitivity of different indices of insulin resistance and their relevance in a clinical setting. MATERIAL AND METHODS: A cross-sectional study of 43 patients with PCOS and 29 noromo ovulatory women as a control group was conducted. Standard clinical, anthropometrical and hormonal testing for hyperandrogenism was conducted, as well as oral glucose tolerance test with determination of basal and stimulated glucose and insulin values. RESULTS: The dynamic I/G index showed the highest sensitivity and specificity, but the static indexes HOMA-IR and QUICKI, although based on only basal glycemic and insulinemic values, showed good sensitivity, 90.38% and 94.01% respectively. HOMA-IR showed significant positive correlation with the stimulated insulin values. CONCLUSIONS: Our results support the use of static indexes in the evaluation of insulin resistance in women with PCOS in a clinical setting, offering a simple assessment of insulin resistance in PCOS, which holds great prognostic and treatment implications.

Tissue-Muscle Perfusion Scintigraphy of the Lower Limbs in a Patient with Type 2 Diabetes Mellitus and Peripheral Arterial Disease.

The estimation of tissue perfusion as a hemodynamic consequence of peripheral arterial disease (PAD) in diabetic patients is of great importance in the management of these patients.We present a noninvasive, functional method of 99mTc-MIBI (methoxy-isobutyl-isonitrile) tissue-muscle perfusion scintigraphy (TMPS) of the lower limbs, which assesses tissue perfusion in basal conditions ("rest" study) and exercise conditions ("stress" study). Emphasis is given on perfusion reserve (PR) as an important indicator of preservation of microcirculation and its local autoregulatory mechanisms in PAD. We present a case of a 71-year-old male diabetic patient with skin ulcers of the right foot and an ankle-brachial index >1.2 (0.9-1.1). Dynamic phase TMPS of the lower limbs showed decreased and late arterial vascularization of the right calf (RC) with lower percentage of radioactivity in the 1st minute: RC 66%, left calf (LC) 84%. PR was borderline with a value of 57% for LC and decreased for RC (42%). Functional assessment of hemodynamic consequences of PAD is important in evaluating both advanced and early PAD, especially the asymptomatic form. The method used to determine the TMPS of the lower limbs, can differentiate subtle changes in microcirculation and tissue perfusion.

Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women.

BACKGROUND: Insulin resistance (IR) is closely associated with diabetes mellitus. On the other hand, increased visceral fat in menopause is also associated with IR, which makes postmenopausal diabetic women in a big risk for cardiovascular diseases. There are conflicting reports about the effects on hormone replacement therapy (HRT) on IR. AIM: The aim of the study was to investigate the effects of HRT on IR. METHODS: A total of 40 postmenopausal women with type 2 diabetes were enrolled and followed for 12 months. Half of them were assigned to take HRT, while the other half made the control group. Fasting plasma glucose (FPG) and insulinemia were measured in both groups at baseline and after 12 months. IR was represented by Homeostatic model assessment for IR (HOMA-IR). RESULTS: HRT was associated with significant decrease in HOMA-IR, FPG and insulinemia in the examined group. There was no significant reduction in FPG and no significant increase in insulinemia levels and HOMA-IR values in control group after 12 months. CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause.

Evaluation of C-Reactive Protein in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with evidence of systemic oxidative stress, activation of circulating inflammatory cells and increased plasma level of proinflamatory cytokines which include C-reactive protein (CRP). CRP is one biomarker of extrapulmonary or systemic consequences of COPD that can be detected. AIM: The aim of this research is to determine whether the level of CRP statistically significantly correlates with the level of bronchial obstruction and the accompanying co-morbidities in patients with COPD. MATERIAL AND METHODS: This study included 80 patients with exacerbation of COPD, hospitalised at the Institute for Lung Diseases and Tuberculosis in Skopje. We measured the level of CRP in the blood in all of these patients in fasting conditions. The classification of COPD patients by the severity of airflow limitation was made according to the actual version of the Global initiative for chronic Obstructive Lung Disease (GOLD). The Student's Independent Samples t-test was used for the statistic analysis of the data. RESULTS: In 52 (65%) of the patients with exacerbation of COPD we detected an increase of the mean value of CRP. The statistical analysis using the Student's t-test showed statistically significant differences in the mean value of CRP in patients with different level of bronchial obstruction. Hypertension, heart failure, diabetes mellitus, hyperlipidemia, coronary disease, and CVI were confirmed as co-morbidities in 45 (73.1%) of the patients, hypertension being the most frequent one (40%). The statistical analysis using the Student's t-test showed statistically significant difference of the mean value of CRP (p< 0.01) depending on the number of co-morbidities. CONCLUSION: In 52 (65%) of the patients with exacerbation of COPD, were detected an increase of the mean value of CRP. The mean values of CRP statistically significantly correlate with the level of bronchial obstruction and the number of co-morbidities in patients with COPD.

Fine Needle Aspiration in Thyroid Nodules - One Year Experience.

AIM: To estimate suspect nodule for benign or malignant characteristics, and to verify cytological features of the node with the fine needle aspiration (FNA) under ultrasound. DESIGN: A total of 106 patients were analyzed. FNA biopsy was performed at outpatient clinic via ultrasound. Inform consent was signed for each patient. Preparation of procedure with local anaesthesia was made by assistant nurse. PROCEDURE: Parallel approach of ultrasound guided fine needle aspiration (USGFNA) was used for each patient. This approach allows the operator to observe needle penetration, location and pathway of the entire needle within the neck, thyroid and nodule, which remain visible on the monitor. As a side effect commonly noticed mild pain and dizziness were recorded. RESULTS: General findings: According the gender, 96 (90.5%) of them were women and 10 (9.5%) men. Median age was 47 ± 9 years. Cytological findings: 5 patients were with papillary carcinoma, 3 with Hurtle cell metaplasia, 1 follicular tumour and 1 with unclear differentiation. CONCLUSION: Close collaboration between endocrinologists, morphologists and surgeons in a multidisciplinary frame is the key to correct preoperative thyroid cancer diagnosis and optimal treatment. FNA biopsy remains the most accurate diagnostic method in detecting thyroid cancer.

Is there a difference in pregnancy and glycemic outcome in patients with type 1 diabetes on insulin pump with constant or intermittent glucose monitoring? A pilot study.

BACKGROUND: The aim of the study is to describe glycemic and insulin outcomes by trimester and maternal and fetal outcome in patients with type 1 diabetes using an insulin pump with constant or intermittent continuous glucose monitoring (CGM). METHODS: Twenty-five women with type 1 diabetes with newly diagnosed pregnancy were treated with insulin pump therapy (Medtronic 722, Medtronic Minimed, Northridge, CA) for at least 1 year. Insulin pump and CGM (Medtronic Paradigm Real-Time) were implemented at least 3 months before conception. Patients were randomized in two groups: constant CGM group, 12 patients on insulin pump with glucose sensor, 24 h/day; and intermittent CGM group, 13 patients on insulin pump with intermittent glucose sensor, 14 days/month. The following parameters were analyzed: glycosylated hemoglobin (HbA1c), mean blood glucose, insulin requirement (in IU/kg/day), weight gain, severe hypoglycemic events, diabetic ketoacidosis, macrosomia, cesarean section, and neonatal hypoglycemia. RESULTS: Both groups achieved good glucose control during their pregnancies (P<0.05): 6.78±1.3% and 6.92±0.9% at the beginning of the study compared with 6.14±0.9% (constant CGM group) and 6.23±0.6% (intermittent CGM group) at the end of the study (last HbA1c before delivery). There was no significant decrease of HbA1c between the two groups. The constant CGM group had a significantly lower A1c in the first trimester compared with the intermittent CGM group. Maternal and fetal outcome did not show a significant difference between the two groups. CONCLUSIONS: Insulin pump therapy together with constant or intermittent CGM can improve diabetes control and pregnancy outcome in type 1 diabetes. The quality of the glucose profile at conception was the important factor for pregnancy outcome.