Comparative Effectiveness of Antidiabetic Drugs as an Additional Therapy to Metformin in Women with Polycystic Ovary Syndrome: A Systematic Review of Metabolic Approaches.

Background: Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause intolerable side effects. Therefore, recent studies have examined the impact of combining metformin with other antidiabetic medications. Methods: A systematic search was performed in Scopus, PubMed, Web of Science, and Embase up to 30 June 2023. All interventional studies that assessed the efficacy of different antidiabetic agents were included. Results: Among the 3488 records found in the primary search, 16 papers were included. Our study showed that dipeptidyl peptidase-4 inhibitors (DPP4i) had the most significant impact on glycemic profile, while thiazolidinediones (TZDs) had the most influence on lipid levels. However, it was observed that patients taking only metformin experienced a greater increase in high-density lipoprotein cholesterol (HDL-C) levels. Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively modified various anthropometric measurements, such as weight, body mass index, waist circumference, and waist-to-hip ratio. The effects of different antidiabetic drugs on hormone levels were inconclusive, although testosterone levels were more affected by GLP1RA, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and TZDs. None of the combined therapies showed a significant change in blood pressure. Conclusion: Since PCOS is a metabolic disorder, choosing the best combination of antidiabetic drugs in the clinical course of PCOS patients will be very important. Today, it seems that we need a new metabolic approach for better treatment of the metabolic aspects of these patients.

Effect of Pioglitazone on Nonalcoholic Fatty Liver Disease in Morbid Obese Patients; a Randomized Controlled Trial.

Background: Nonalcoholic fatty liver disease (NAFLD) is a common obesity-related disease. In this study, we aimed to investigate the effects of pioglitazone on NAFLD in morbid obese patients. Materials and Methods: This is a randomized controlled trial study that was performed in 2020-2021 on 44 patients who had grade 3 NAFLD. At the beginning of the study, we collected the following data: age, gender, body mass index (BMI), fasting blood glucose (FBS), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), and the total size and volume of the liver and the left lobe of the liver. Patients in the control group were given a special diet. For patients in the treatment group, pioglitazone 15 mg tablets were administered twice daily for 4 months. Results: At the beginning of the study, all patients in both groups had grade 3 of NAFLD. After the treatments, 50% of the pioglitazone group had grade 1 NAFLD, and 50% of other patients had grade 2 that showed significant improvements in patients (P < 0.001). We also found significant improvements in the following items in the intervention group: liver size (P < 0.001), size of the left liver lobe (P < 0.001), FBS (P = 0.036), ALT (P = 0.011), and BMI (P < 0.001). No significant improvements were found in the control group (P > 0.05). Conclusion: The use of pioglitazone for 4 months resulted in improvements in fatty liver stage, liver size, BMI, FBS, and lipid profile. These data show the effectiveness of pioglitazone in NAFLD.

Effect of sitagliptin on proteinuria in patients with type 2 diabetes - A renoprotective effect of sitagliptin.

BACKGROUND: Diabetic nephropathy, the leading cause of chronic renal failure, is related to diabetes poor control. Some antihyperglycemic drugs like dipeptidyl peptidase-4 inhibitors have shown to prevent diabetic nephropathy. This study endeavors to assess the effect of sitagliptin on proteinuria in Iranian type 2 diabetics. MATERIALS AND METHODS: A total of 90 type 2 diabetic patients aged between 30 and 80 years with glycated hemoglobin (HbA1C) <8.5 and normotensive under treatment of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were randomly assigned into two groups. One group received 50 mg sitagliptin per day and the other group received placebo. The two groups were evaluated for albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) at baseline and 3 months later. RESULTS: Eighty-four patients, 38 (45%) males and 46 (55%) females, were enrolled in this study. The mean age was 58.47 ± 7.33. The two groups did not differ in baseline characteristics. After 3 months, in the sitagliptin group, HbA1C (7.89 ± 0.39 to 7.37 ± 0.61, P < 0.001), fasting blood sugar (FBS) (136.86 ± 22.51 to 130.53, P = 0.04), systolic blood pressure (BP) (124.39 ± 9.70 mmHg to 119.32 ± 9 mmHg), diastolic BP (76.44 ± 6.53 to 73.13 ± 5.34 mmHg, P < 0.001), and ACR (314.40 ± 414.64 to 293.49 ± 400.71, P < 0.001) were significantly decreased and eGFR was significantly increased (73.35 ± 10.73 to 76.86 ± 10.59, P < 0.001) at 3 months compared to the placebo group. ACR reduction was higher in macroalbuminuric (Ma) patients compared to microalbuminuric (Mi) patients in the sitagliptin group (-30.25 ± 35.57 vs. -11.12 ± 14.01, P = 0.02). No significant difference was observed between the Ma and Mi subgroups regarding changes in eGFR. Univariate analysis showed that changes in ACR correlated with FBS (r = 0.68, P < 0.0001), insulin (r = 0.44, P = 0.03), and homeostatic model assessment for insulin resistance (r = 0.69, P < 0.0001) and did not correlate with eGFR and BP. CONCLUSION: In conclusion, sitagliptin is a well-tolerated drug that improves glycemic control, lowers BP, and reduces urinary albumin excretion, especially in Ma type 2 diabetic patients.

Assessment and comparison of the antioxidant defense system in patients with type 2 diabetes, diabetic nephropathy and healthy people: A case-control study.

INTRODUCTION: Findings of previous studies in the field of antioxidant defense system in patients with type 2 diabetes (T2DM), diabetic nephropathy (DM) are limited and conflicting. Therefore, we evaluated the antioxidant defense system status in type 2 diabetes patients, diabetic nephropathy and healthy subjects in Iranian population. METHODS: This population-based case-control study was conducted in 2019 and included 30 individuals with T2DM and 30 patients with DN, as the case groups and 30 healthy subjects for the control group. Individuals entered to the study for case group were diagnosed as T2DM patients based on fast glucose blood tests (FGB) (≥126 mg/dL) and HbA1 (≥6.5%). DN was defined based on these tests and macroalbuminuria (>300 mg/day). Serum was carefully separated and antioxidant defense system status was estimated. Dietary intakes were evaluated by using a food frequency questionnaire (FFQ). RESULTS: Energy intake in control group was higher than case groups; BMI was higher in the DN group compared to the other groups. Significantly higher levels of MDA were observed in T2DM patients compared to control group in crude model (1.255 vs. 1.079 nmol/L; P = 0.006). The same results were shown after adjustment for potential confounders (1.256 vs. 1.085 nmol/L; P = 0.022). Total antioxidant capacity (TAC) was less in case groups compared with control group; level of catalase (CTL) and superoxide dismutase enzymes comparisons showed that DN patients had higher level than control group, but these associations were not significant. CONCLUSIONS: We found that MDA levels were significantly higher in T2DM patients compared to control group. Level of TAC was less in case groups in comparison to controls. SOD and CTL levels were higher in DN compared to controls; these associations were not significant.

A rare enzymatic defect, true isolated 17,20-lyase deficiency leading to endocrine disorders and infertility: case report.

The cytochrome P450 17A1 catalyzes the formation of 17-hydroxysteroids and 17-ketosteroid. Most defects in CYP17A1 impair both enzymatic activities and cause a combined 17α-hydroxylase/17,20-lyase deficiency, which impairs hormone production (cortisol and sex steroids), sexual development, and puberty. Isolated 17,20-lyase deficiency is usually defined by evidently normal activity of 17α-hydroxylase with a dramatic decline of 17,20-lyase activity or complete inactivity. The changes in enzyme activity lead to a lack in the production of sex steroids with normal levels of glucocorticoid and mineralocorticoid hormones. A 24-years-old married woman, as a product of a consanguineous marriage, presented with infertility and a background marked by primary amenorrhea. Laboratory data showed low normal serum cortisol levels and low levels of 17-hydroxyprogesterone. Also, her adrenal androgens were low but estradiol was normal. The chromosomal investigation uncovered a male karyotype of 46, XY. These clinical and laboratory evidence confirm the determination of an isolated 17,20-lyase deficiency in a genotypic male.

Acromegaly and papillary thyroid carcinoma: A case series.

Acromegaly is a rare chronic disease and associated with an increased risk of malignancy. The issue of the risk of thyroid cancer in these patients is a topic of debate, and the number of large case-control studies is very limited. Several studies indicated that a chronic excess insulin-like growth factor-1 stimulates the proliferation of various cell types and induces an antiapoptotic effect in thyroid follicular cells. In the literature, the risk of thyroid cancer was reported greater than five-fold. In this review, we will briefly summarize the studies available regarding thyroid cancer in patients with acromegaly and present three case reports.

Alendronate improves fasting plasma glucose and insulin sensitivity, and decreases insulin resistance in prediabetic osteopenic postmenopausal women: A randomized triple-blind clinical trial.

AIMS/INTRODUCTION: Postmenopausal women receive bisphosphonates for osteoporosis treatment. The effect of these medications on developing diabetes mellitus in prediabetic patients is yet to be investigated. We aimed to determine the effect of alendronate on plasma glucose, insulin indices of postmenopausal women with prediabetes and osteopenia. MATERIALS AND METHODS: The present triple-blind randomized controlled clinical trial included 60 postmenopausal women, aged 45-60 years. All patients were vitamin D sufficient. They were randomly enrolled in intervention (70 mg/week alendronate for 12 weeks) and control (placebo tablet per week for 12 weeks) groups. The morning 8-h fasting blood samples were collected at the baseline and follow-up visits to measure the fasting plasma glucose (mg/dL), insulin and hemoglobin A1c (HbA1c). Plasma glucose and insulin concentration were measured 30, 60 and 120 min after the glucose tolerance test. The Matsuda Index, homeostasis model assessment of insulin resistance, homeostasis model assessment of ß-cell function and the area under the curves of glucose and insulin were calculated. RESULTS: The mean (standard deviation) fasting plasma glucose (102.43 [1.46] mg/dL vs 94.23 [1.17] mg/dL, P = 0.001), 120-min insulin concentration (101.86 [15.70] mU/L vs 72.60 [11.36] mU/L, P = 0.026), HbA1c (5.60 [0.06]% vs 5.40 [0.05]%, P = 0.001), homeostasis model assessment of insulin resistance (3.57 [0.45] vs 2.62 [0.24], P = 0.021) and Matsuda Index (7.7 [0.41] vs 9.2 [0.4], P = 0.001) significantly improved in the alendronate-treated group. There were more statistically significant reductions in fasting plasma glucose (-8.2 [8.63] mg/dL vs -2.5 [14.26] mg/dL, P = 0.002) and HbA1c (-0.2 [0.23]% vs -0.09 [0.26]%, P = 0.015) observed in the alendronate-treated group than the placebo group during the study course, respectively. CONCLUSIONS: Administration of 70 mg/week alendronate improves fasting plasma glucose, HbA1c and insulin indices in postmenopausal women.

Effect of Helicobacter pylori eradication on insulin resistance among prediabetic patients: A pilot study and single-blind randomized controlled clinical trial.

BACKGROUND: Type II diabetes mellitus (T2DM) is the prevalent type of diabetes in the world. Prediabetic patients are the most probable group to get diabetes. Several studies have mentioned the role of inflammation in the incidence of diabetes. The origin of inflammation can be infection such as Helicobacter pylori (HP) infection. This study was designed to explore the effect of HP eradication on insulin resistance. MATERIALS AND METHODS: This single-blind randomized controlled clinical trial was conducted in 2014-2015. The sample size consisted of 49 individuals who were in prediabetes stage with HP infection. Patients with positive stool antigen were allocated randomly into two groups. The treatment group took medication to eradicate HP infection by the routine method of four-drug eradication. However, placebo capsules and tablets were given to the patients in the placebo group. Then fasting plasma glucose (FPG), fasting plasma insulin (FPI), and quantitative C-reactive protein (CRP) levels were measured and homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta-cell function (HOMA-B), Matsuda index, insulinogenic index, and disposition index were calculated. RESULTS: Results of this study showed that FPI and HOMA-IR increased significantly (P value of FPI = 0.023 and P value of HOMA-IR = 0.019) after HP eradication in the treatment group. On the other hand, comparison of differences at the baseline and after 6 weeks in FPG (P value = 0.045), FPI (P value = 0.013), and HOMA-B (P value = 0.038) revealed significant differences between the placebo group and treatment group. CONCLUSION: Results showed that HP eradication by a 2-week antibiotic medication did not decrease insulin resistance and even increased FPI and insulin resistance indices. So HP eradication among prediabetic patients is not recommended for the decrease of insulin resistance and postponement of the development of diabetes mellitus.

Effects of Levothyroxine and thyroid stimulating hormone on bone loss in patients with primary hypothyroidism.

OBJECTIVE: Previous studies on bone mineral density (BMD) abnormalities associated with hypothyroidism are scarce and not conclusive. The effect of thyroid hormone therapy on BMD has shown mixed results. The aim of the present study was to determine the severities of osteoporosis in female patients with hypothyroidism in comparison to healthy women. METHODS: This cross-sectional descriptive study was performed on 150 women aged over 50 years. Totally, 100 patients with primary hypothyroidism and 50 healthy subjects were enrolled in this study and divided into three groups. Group A, which consisted the patients who had been recently diagnosed with primary hypothyroidism. The second group of patients diagnosed with primary hypothyroidism for at least 2 years and was treated with levothyroxine (Group B). The third group of healthy individuals was selected as a control group (Group C). Blood samples were taken for the measurements of thyroid stimulating hormone (TSH), and bone densitometry was performed to determine the BMD reported as T-score in order to measure the severity of osteoporosis. T-score of the lumbar vertebra (L2-L4) and femoral neck were measured with dual energy X-ray absorptiometry and were compared between the three groups. Data were analyzed by SPSS using regression analysis and Mann-Whitney, Kruskal-Wallis, or analysis of variances statistical tests. The statistical significance was set at a P < 0.05. FINDINGS: The average age of patients and baseline serum TSH levels in Group B was significantly different from the other two groups (P < 0.001). T-score of the lumbar spine (L2-L4) in Group B was significantly lower than the other groups (P = 0.01). The linear regression between serum TSH levels and BMD categories were not clearly associated. However, after removing the effect of the baseline TSH level in Group B, bone loss was significantly greater than the other two groups (P = 0.01). CONCLUSION: According to the present study, it seems that the treatment of hypothyroidism with thyroid hormones reduces both serum levels of TSH and bone density. Hence, proper control of this risk factor can be an effective way in prevention of osteoporosis.

The effects of non-attendance information therapy on the control of glycosylated hemoglobin (HbA1C) in type 2 diabetic patients.

INTRODUCTION: Patient education plays an important role in the control of diabetes. Nonattendance education, enabling elimination of limitations caused by time and space and facilitating the relationship between patient and care liaison is an effective, simple, and cheap method. The aim of this study is determination of the effects of nonattendance information therapy on the control of glycosylated hemoglobin (HbA1C) in type 2 diabetic patients in Isfahan. MATERIALS AND METHODS: The present study was an interventional semi experimental study with pretest and post-test and control groups. Statistical population were type 2 diabetics patients of the Isfahan Endocrine and Metabolism Research Center, of whom 64 people were randomly selected and divided into intervention and control groups. First, the preliminary data were collected using the HbA1c test in patients. Then, the intervention group received training package and Short Message Service (SMS) for eight weeks. After one-month incubation period, HbA1c was again determined in both groups. Data were analyzed using t-test, paired t-test and Mann-Whitney U and Chi-square tests. RESULTS: Results showed that diabetes patients' HbA1c in the intervention group was significantly lower after the intervention through training packages and SMS service compared to before the intervention (P < 0.001). Comparison of the two groups showed that there was a significant difference in the HbA1C between the intervention and control groups (P = 0.048). CONCLUSION: Follow-up of education of patients with type 2 diabetes through training packages and SMS services had significant effects on the control of the patients' HbA1C. Also due to the low cost and high effectiveness of this method, it is recommended to health-care providers and treatment groups. This study also showed that having medical librarians along with treatment group can have a positive effect on the type 2 diabetic patients' health.

Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome.

INTRODUCTION: Hypothyroidism is associated with pregnancy complications both for the mother and progeny and it should be considered in reproductive age. Thyroid autoimmunity is stated to be the main cause of hypothyroidism in iodine sufficient areas. Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder affecting women in reproductive age. Early diagnosis and treatment of hypothyroidism in PCOS may reduce the rate of infertility and pregnancy-related morbidity. In the present study we evaluated thyroid autoimmunity in PCOS patients. METHODS: Over a period of 12 months, 78 patients with PCOS were recruited to this case-control study. Three hundred and fifty age-matched women were studied as a control group. PCOS was defined according to the revised 2003 Rotterdam criteria. Thyroid size was estimated by inspection and palpation. Serum thyroid stimulating hormone (TSH), anti-thyroperoxidase antibody (anti-TPO Ab), and anti-thyroglobulin antibody (anti-Tg Ab) were measured. RESULTS: The mean ± SD of serum anti-TPO Ab in PCOS patients and subjects in the control group was 216 ± 428 and 131 ± 364 IU/mL, respectively (P = 0.04). Prevalence of goiter in PCOS patients was higher than that in control subjects (62.3 vs. 35.7%, P = 0.0001). Serum TSH and anti-Tg Ab in PCOS patients and control subjects did not differ significantly. CONCLUSION: In this case-control study, anti-thyroid antibodies and goiter prevalence were significantly higher in PCOS patients. These data suggest that thyroid exam and evaluation of thyroid function and autoimmunity should be considered in such patients.

Residual goiter in Semirom; iodine status and thiocyanate overload do not play a role.

This study was performed to investigate the role of thiocyanate overload in the etiology of endemic goiter in schoolchildren of Semirom, Iran. A total of 1828 schoolchildren were selected by multi-stage random sampling. Urinary iodine concentration (UIC) and urinary thiocyanate (USCN) were measured in a group of these children. The median UIC was 18.5 microg/dl. The mean +/- SD of USCN in goitrous and nongoitrous subjects did not differ significantly (0.75 +/- 0.78 mg/dl vs. 0.63 +/- 0.40 mg/dl; p = 0.30). Finally, we concluded that neither iodine deficiency nor thiocyanate overload contributed to the high prevalence of goiter in Semirom. The role of other goitrogenic factors should be investigated in this region.

Zinc status in goitrous school children of Semirom, Iran.

BACKGROUND: Iodine deficiency produces the spectrum of iodine deficiency disorders (IDDs) including endemic goiter, hypothyroidism, cretinism and congenital anomalies. Other factors, including goitrogens and micronutrient deficiencies may influence the prevalence and severity of IDDs and response to iodine supplementation. An association between zinc and goiter has previously been reported. METHODS: A cross sectional study investigating an association between goiter and serum zinc status was performed in 2003 in a mountainous region of Iran. One thousand eight hundred twenty-eight children were selected by multistage cluster sampling. Goiter staging was performed by inspection and palpation. Serum zinc, total thyroxine, thyroid stimulating hormone and urinary iodine concentration were measured in a group of these children. RESULTS: Thirty six and seven tenth percent of subjects were classified as goitrous. Serum zinc level in goitrous and nongoitrous children was 82.80 ± 17.85 and 83.38 ± 16.25 µg/dl, respectively (p = 0.81). The prevalence of zinc deficiency (serum zinc ≤65 µg/dl) in goitrous and nongoitrous children did not differ significantly (9.3 % vs. 10.8%, p = 0.70). CONCLUSIONS: Goiter is still a public health problem in Semirom. According to the present study zinc status may not play a role in the etiology of goiter in Semirom school children. However, the role of other goitrogens or micronutrient deficiencies should be investigated in this region.

Increased insulin sensitivity by metformin enhances intense-pulsed-light-assisted hair removal in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an insulin-resistant state with hirsutism as a common manifestation. OBJECTIVE: We hypothesized that treatment with metformin would improve the cosmetic effects of intense pulsed light (IPL) therapy for hair removal in PCOS patients. METHODS: In a prospective randomized controlled trial, 70 PCOS patients randomly received metformin (1,500 mg daily) + IPL therapy or IPL therapy alone for 5 IPL sessions during a 6-month period, followed by an additional 6 months of observation. Hirsutism score, homeostasis model assessment for insulin resistance (HOMA-IR), free androgen index (FAI) and patient satisfaction were evaluated at every visit. RESULTS: Fifty-two patients finished the study. Hirsutism was significantly better controlled in the metformin group (p = 0.009). Patient satisfaction was significantly better in the metformin group at the end of the observation period (52.9 vs. 34.1%, p = 0.019). HOMA-IR and FAI scores improved after metformin + IPL treatment (p < 0.05). CONCLUSION: Adding metformin to IPL in women with PCOS results in a significant improvement in insulin sensitivity and hirsutism.

Endemic goiter in Semirom; there is no difference in vitamin A status between goitrous and nongoitrous children.

BACKGROUND: Despite long-standing iodine supplementation in Iran, the prevalence of goiter remains high in some areas. This suggests other nutritional deficiencies may be considered as responsible factors for goiter persistence. In the present study we investigated the possible role of vitamin A deficiency (VAD) and low vitamin A status in the etiology of endemic goiter in Semirom, Iran. MATERIALS AND METHODS: In this cross-sectional study, 1,828 students from 108 primary schools of urban and rural areas of Semirom were selected by multistage random cluster sampling. Thyroid size was estimated in each child by inspection and palpation. Urinary iodine concentration (UIC) and serum retinol (SR) were measured. RESULTS: Overall, 36.7% of schoolchildren had goiter. The median UIC was 18.5 microg/dL. The mean+/-SD of SR in goitrous and nongoitrous children was 38.84+/- 10.98 and 39.17+/-10.85 microg/dL respectively (p=0.82). There were two children with VAD (SR less than 20 microg/dL); one in the goitrous and one in the nongoitrous group. The prevalence of subjects with low vitamin A status (SR less than 30 microg/dL) in the goitrous and nongoitrous groups was 26.2 and 21.5% respectively (p=0.42). CONCLUSION: Goiter is still a public health problem in this region. Iodine deficiency, VAD or low vitamin A status is not among the contributors of goiter persistence in schoolchildren of Semirom. The role of other micronutrient deficiencies or goitrogens should be investigated.

Iron deficiency in goitrous schoolchildren of Semirom, Iran.

BACKGROUND: Iodine deficiency produces the spectrum of iodine deficiency disorders (IDDs): endemic goiter, hypothyroidism, cretinism, and congenital anomalies. Other factors, including goitrogens and micronutrient deficiencies, may influence the prevalence and severity of IDDs and response to iodine supplementation. This cross-sectional, descriptive study was performed in 2003 on elementary school children of Semirom, a mountainous region of Iran, where goiter was hyper-endemic in 1994, but the goiter prevalence had not decreased as expected many years after salt iodization and iodine injection. Some possible risk factors associated with goiter in that area were evaluated, and the results of iron study are presented here. METHODS: 1,869 cases were selected by a multistage cluster sampling procedure. Grade 2 goitrous children were compared with equal number of nongoitrous children for serum iron, ferritin, transferrin, thyroxin, TSH and urine iodine concentrations (UIC). RESULTS: 210 children (105 goiter grade 0 and 105 goiter grade 2) entered this sub-study. Of 210 participants, 70 children had low transferrin saturation, 13 had low serum ferritin and 9 children had both problems. There was no significant difference in goiter rate between children with low iron indices and others. There was no significant correlation between serum iron, ferritin or transferrin saturation with other variables including T4, UIC and goiter stage. CONCLUSION: The present study reveals that in the area studied, iron deficiency cannot explain the high prevalence of goiter, so other responsible factors should be investigated.