Characteristics of diabetes mellitus patients in Turkey: An analysis of national electronic health records.

BACKGROUND: It was estimated that there were 537 million people with diabetes mellitus in 2021, representing 10.5% of the global adult population. Diabetes prevalence in Turkey is 13.5%, according to a meta-analysis and 17.3% according to a recent study. Although the primary purpose of Electronic Health Records (EHRs) is clinical, researchers can use them to conduct epidemiologic investigations. This study aims to document the prevalence of diabetes and to evaluate the healthcare utilization of people with diabetes compared to the people without diabetes, based on national EHR. METHODS: Only people over 14 years old were included in the analysis. Our criteria for being diabetic were 1) having an HbA1c over 6.5% (48 mmol/mol), 2) having a prescription with DM diagnosis, ICD-10 codes E10-E14, or 3) having at least two fasting blood glucose measurements over 126 mg/dl. RESULTS: At the end of 2020, there were 7,178,674 individuals with diabetes, with 11.12% prevalence, 13.10% in women while 9.12% in men. Age-adjusted healthcare facility admission per capita was 15.5 for people with diabetes, 9.5 for people without diabetes, while the number of prescriptions was 7.9 for people with diabetes while 4.5 for people without diabetes in 2019. The mean number of prescriptions containing antidiabetics was 2.88 per person with diabetes in 2019. DISCUSSION: Approximately 11% of Turkish people have diagnosed with diabetes. We estimate that about one-third of people with diabetes are undiagnosed and the majority of these people are men. The results show that such large databases have the capability of supplying a vast amount of information to the scientific community.

Generation of a Beta-Cell Transplant Animal Model of Diabetes Using CRISPR Technology.

Since insulin deficiency results from pancreatic beta-cell destruction, all type 1 and most type 2 diabetes patients eventually require life-long insulin injections. Insulin gene synthesis could also be impaired due to insulin gene mutations as observed in diabetic patients with MODY 10. At this point, insulin gene therapy could be very effective to recompense insulin deficiency under these circumstances. For this reason, an HIV-based lentiviral vector carrying the insulin gene under the control of insulin promoter (LentiINS) was generated, and its therapeutic efficacy was tested in a beta-cell transplant model lacking insulin produced by CRISPR/Cas9-mediated genetically engineered pancreatic beta cells. To generate an insulin knockout beta-cell transplant animal model of diabetes, a dual gene knockout plasmid system involving CRISPR/Cas9 was transfected into a mouse pancreatic beta cell line (Min6). Fluorescence microscopy and antibiotic selection were utilized to select the insulin gene knockout clones. Transplantation of the genetically engineered pancreatic beta cells under the kidney capsule of STZ-induced diabetic rats revealed LentiINS- but not LentiLacZ-infected Ins2KO cells transiently reduced hyperglycemia similar to that of MIN6 in diabetic animals. These results suggest LentiINS has the potential to functionally restore insulin production in an insulin knockout beta-cell transplant animal model of diabetes.

Management of diabetic foot ulcers and the challenging points: An endocrine view.

Diabetic foot ulcers (DFU) are one of the most challenging complications of diabetes. Up to one-third of patients with diabetes mellitus (DM) may suffer from DFUs during their life. DFU is one of the leading causes of morbidity in patients with DM. The treatment period is challenging, and the recurrence rate of DFUs is high. Hence, establishing prevention strategies is the most important point to be emphasized. A multidisciplinary approach is necessary in the prevention and treatment of DFUs. Patients at risk should be identified, and prevention measures should be taken based on the risk category. Once a DFU is formed, the appropriate classification and evidence-based treatment interventions should be executed. Glycemic control, diagnosis and treatment of vascular disease, local wound care, diagnosis, and treatment of infection should be addressed along with the proper evaluation and management of general health status.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Clinical Characteristics and Follow-Up Results of Adrenal Incidentaloma.

It is recommended that adrenal incidentaloma patients should be monitored for radiological changes, increase in size and new functionality that may occur in the future, even if they are benign and nonfunctional at the initial evaluation. Our aim is to evaluate the key clinical characteristics of adrenal incidentaloma patients focusing on changes during follow-up and associated clinical outcomes. A total of 755 patients (median age: 56 years), with an adrenal incidentaloma > 1 cm and underwent functionality tests, were included in the study. Clinical characteristics, functionality status and follow-up durations were recorded. During the course of follow-up, any changes in size and development of new functionality, and clinical consequences thereof were evaluated. In 71.8% of patients, incidentalomas were non-functional. Most frequent functionality (15.8%, n=119) was subclinical hypercortisolemia (SH) [10.9% (n=82) possible autonomous cortisol secretion (PACS) and 4.9% (n=37) autonomous cortisol secretion (ACS)] of all incidentalomas. Frequencies of Cushing's syndrome (CS), pheochromacytoma and primary hyperaldosteronism were 4.9% (n=37), 3.8% (n=29) and 3.7% (n=28), respectively. Adrenocortical carcinoma frequency was 1.5% (n=11). Of 755 patients, 43% (n=325) were followed up regularly more than 6 months. Median follow-up duration was 24 months (6-120). A total of 17 (5.2%) patients, which had non-functional incidentalomas at baseline had developed new functionality during follow-up, of which 15 (4.6%) were SH [13 patients (4%) PACS and 2 patients (0.6%) ACS] and 2 (0.6%) were CS. During follow-up, 24% (n=78) of the patients had an increase in mass size between 5-9 mm, while 11.7% (n=38) of the patients had an increase of ≥10 mm. During follow-up, 4% (n=13) of the patients developed a new lesion with a diameter ≥10 mm on the opposite side. In patients with a follow-up duration of more than 2 years, frequencies of size increase and new lesion emerging at the opposite adrenal gland were higher. 14 patients (4.3% of the patients with regular follow-up) underwent surgery due to increase in size or development of new functionality during follow-up. Our study demonstrated that a necessity for surgery may arise due to increase in size and development of functionality during follow-up period in adrenal incidentaloma patients, and thus continuing patient follow-up, even with wider intervals, will be appropriate.

Lentiviral gene therapy vectors encoding VIP suppressed diabetes-related inflammation and augmented pancreatic beta-cell proliferation.

Type 1 diabetes (T1DM) is an autoimmune condition in which the immune system attacks and destroys insulin-producing beta cells in the pancreas leading to hyperglycemia. Vasoactive intestinal peptide (VIP) manifests insulinotropic and anti-inflammatory properties, which are useful for the treatment of diabetes. Because of its limited half-life due to DPP-4-mediated degradation, constant infusions or multiple injections are needed to observe any therapeutic benefit. Since gene therapy has the potential to treat genetic diseases, an HIV-based lentiviral vector carrying VIP gene (LentiVIP) was generated to provide a stable VIP gene expression in vivo. The therapeutic efficacy of LentiVIP was tested in a multiple low-dose STZ-induced animal model of T1DM. LentiVIP delivery into diabetic animals reduced hyperglycemia, improved glucose tolerance, and prevented weight loss. Also, a decrease in serum CRP levels, and serum oxidant capacity, but an increase in antioxidant capacity were observed in LentiVIP-treated animals. Restoration of islet cell mass was correlated with an increase in pancreatic beta-cell proliferation. These beneficial results suggest the therapeutic effect of LentiVIP is due to the repression of diabetes-induced inflammation, its insulinotropic properties, and VIP-induced beta-cell proliferation.

Lentivirus Mediated Pancreatic Beta-Cell-Specific Insulin Gene Therapy for STZ-Induced Diabetes.

Autoimmune destruction of pancreatic beta cells is the characteristic feature of type 1 diabetes mellitus. Consequently, both short- and intermediate-acting insulin analogs are under development to compensate for the lack of endogenous insulin gene expression. Basal insulin is continuously released at low levels in response to hepatic glucose output, while post-prandial insulin is secreted in response to hyperglycemia following a meal. As an alternative to multiple daily injections of insulin, glucose-regulated insulin gene expression by gene therapy is under development to better endure postprandial glucose excursions. Controlled transcription and translation of proinsulin, presence of glucose-sensing machinery, prohormone convertase expression, and a regulated secretory pathway are the key features unique to pancreatic beta cells. To take advantage of these hallmarks, we generated a new lentiviral vector (LentiINS) with an insulin promoter driving expression of the proinsulin encoding cDNA to sustain pancreatic beta-cell-specific insulin gene expression. Intraperitoneal delivery of HIV-based LentiINS resulted in the lowering of fasting plasma glucose, improved glucose tolerance and prevented weight loss in streptozoticin (STZ)-induced diabetic Wistar rats. However, the combinatorial use of LentiINS and anti-inflammatory lentiviral vector (LentiVIP) gene therapy was required to increase serum insulin to a level sufficient to suppress non-fasting plasma glucose and diabetes-related inflammation.

Cytopathology-histopathology correlation and the effect of nodule diameter on diagnostic performance in patients undergoing thyroid fine-needle aspiration biopsy.

INTRODUCTION: Although thyroid fine-needle aspiration biopsy (FNAB) is established to have a good overall sensitivity and specificity, various outcomes have been reported on its performance in large nodules. The aim of the study was to evaluate the diagnostic performance of FNAB and the effect of the nodule diameter on its diagnostic performance. MATERIALS AND METHODS: The outcomes of a total of 7319 patients who underwent FNAB over the course of 5 years were analyzed retrospectively and 648 patients who had undergone post-FNAB thyroidectomy or lobectomy were included in the study. FNAB results were classified according to the Bethesda system. After evaluating the compatibility between cytology and pathology results, all-nodules and diameter-based (<4 cm and ≥4 cm) sensitivity, specificity, false positivity, false negativity, and accuracy rates of FNAB were calculated. RESULTS: Sensitivity of FNAB was 85.4% for all nodules, 88.3% for nodules <4 cm, and 75.8% for nodules >4 cm (P < 0.001). Specificity was 58.4% for all nodules, 49.3% for nodules <4 cm, and 75.1% for nodules >4cm (P < 0.001). While false positivity was 41.6% for all nodules, it was 50.7% for nodules smaller than 4 cm and was 24.9% for nodules larger than 4 cm (P < 0.001). False negativity was 14.6% for all nodules and was 11.7% for nodules smaller than 4 cm and 24.2% for nodules larger than 4 cm (P < 0.001). Finally, among the entire set of nodules, the accuracy was 64.4%, which was 59.2% in nodules smaller than 4 cm, and 75.2% in nodules larger than 4 cm (P < 0.001). CONCLUSION: Despite a higher rate of false negativity, FNAB has higher specificity and accuracy in large nodules than those in the small nodules. Nodule diameter should not be used alone as a criterion to recommend thyroidectomy to the patient.

Utilization of statins and LDL-cholesterol target attainment in Turkish patients with type 2 diabetes - a nationwide cross-sectional study (TEMD dyslipidemia study).

BACKGROUND: Attaining acceptable levels of LDL Cholesterol (LDL-C) significantly improves cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM). The LDL-C target attainment and the characteristics of patients attaining these targets were investigated in this study. Furthermore, the reasons for not choosing statins and the physicians' attitudes on the treatment of diabetic dyslipidemia were also examined. METHODS: A nationwide, cross-sectional survey was conducted in tertiary centers for diabetes management. Adult patients with T2DM, who were under follow-up for at least a year in outpatient clinics, were consecutively enrolled for the study. LDL-C goals were defined as below 70 mg/dL for patients with macrovascular complications or diabetic nephropathy, and below 100 mg/dL for other patients. Data about lipid-lowering medications were self-reported. RESULTS: A total of 4504 patients (female: 58.6%) were enrolled for the study. The mean HbA1c and diabetes duration was 7.73 ± 1.74% and 10.9 ± 7.5 years, respectively. The need for statin treatment was 94.9% (n = 4262); however, only 42.4% (n = 1807) of these patients were under treatment, and only 24.8% (n = 448) of these patients achieved LDL-C targets. The main reason for statin discontinuation was negative media coverage (87.5%), while only a minority of patients (12.5%) mentioned side effects. Physicians initiated lipid-lowering therapy in only 20.3% of patients with high LDL-C levels. It was observed that the female gender was a significant independent predictor of not attaining LDL-C goals (OR: 0.70, 95% CI: 0.59-0.83). CONCLUSIONS: Less than 50 % of patients with T2DM who need statins were under treatment, and only a quarter of them attained their LDL-C targets. There exists a significant gap between the guideline recommendations and the real-world evidence in the treatment of dyslipidemia in T2DM.

Development of therapeutic options on type 2 diabetes in years: Glucagon-like peptide-1 receptor agonist's role intreatment; from the past to future.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hypergly-cemia. Type 2 diabetes (T2DM) accounting for 90% of cases globally. The worldwide prevalence of DM is rising dramatically over the last decades, from 30 million cases in 1985 to 382 million cases in 2013. It's estimated that 451 million people had diabetes in 2017. As the pathophysiology was understood over the years, treatment options for diabetes increased. Incretin-based therapy is one of them. Glucagon-like peptide-1 receptor agonist (GLP-1 RA) not only significantly lower glucose level with minimal risk of hypoglycemia but also, they have an important advantage in themanagement of cardiovascular risk and obesity. Thus, we will review here GLP-1 RAsrole in the treatment of diabetes.

Diagnostic value of the late-night salivary cortisol in the diagnosis of clinical and subclinical Cushing's syndrome: results of a single-center 7-year experience.

Late-night salivary cortisol (LNSaC) is an easy-to-use test reflecting the free cortisol level in the serum and does not require hospitalization. Controlled studies reported that LNSaC has a high sensitivity and specificity, but have not set a clearly defined cut-off value to be used in the diagnosis of Cushing's syndrome. In this study, we aimed to evaluate the diagnostic performance of LNSaC in patients with clinical Cushing's syndrome (CCS) and subclinical Cushing's syndrome (SCS). The data of 543 patients, whose LNSaC levels were assessed using electrochemiluminescence immunoassay method, were retrospectively evaluated. The study included a total of 324 patients: 58 patients with CCS, 53 patients with SCS, and 213 patients without Cushing's syndrome (NoCS). The cause of the Cushing's syndrome was hypophyseal in 26 patients (45%), adrenal in 24 patients (41%), and ectopic in 8 patients (14%) in the CCS group. Median LNSaC levels were 0.724 (0.107-33) µg/dL in CCS group, 0.398 (0.16-1.02) µg/dL in SCS group, and 0.18 (0.043-0.481) µg/dL in NoCS group (p=0.001). Accordingly, LNSaC had 89.6% sensitivity and 81.6% specificity at a cut-off value of 0.288 µg/dL in the diagnosis of CCS; and had 80.7% sensitivity and 85.1% specificity at a cut-off value of 0.273 µg/dL in the diagnosis of SCS. In the present study, a lower sensitivity and specificity than previously reported was found for LNSaC in the diagnosis of CCS. Moreover, the diagnostic performance of LNSaC in patients with SCS was close to its diagnostic performance in patients with CCS. Each center should determine its own cut-off value based on the method adopted for LNSaC measurement, and apply that cut-off value in the diagnosis of Cushing's syndrome.

Cystic lateral neck mass: Thyroid carcinoma metastasis to branchial cleft cyst.

Etiologies of lateral cervical masses are complex, most commonly these masses are branchial cleft cysts; however, metastatic thyroid carcinoma should be included in the differential. We report a case of lateral cystic neck mass in a 22-year-old female patient diagnosed as metastatic papillary thyroid carcinoma. The patient was diagnosed after she underwent surgery for branchial cleft cyst. The patient underwent thyroidectomy which revealed multifocal micropapillary thyroid carcinoma with capsular invasion and lymph node metastases. Radioactive iodine treatment was planned. Congenital malformations of the lateral neck may present themselves in the second and third decades of life. Ectopic thyroid tissue within a branchial cleft cyst may give rise to primary papillary carcinoma, as well as branchial cleft cyst may harbor metastases of primary thyroid papillary carcinoma. We classified our patient as a metastasis to the branchial cleft cyst rather than primary papillary carcinoma of the branchial cleft cyst.

Bone metastases without primary tumor: A well-differentiated follicular thyroid carcinoma case.

Metastases to the bone are the most common malignant bone tumors. Prostate, breast, and lung carcinomas are the most common primaries of bone metastases. Bone metastases show poor prognosis in means of median survival; however, some patients with highly curable tumors such as thyroid carcinoma may benefit from treatment. We report and discuss a unique case of a 70-year-old female patient presenting with arm pain, diagnosed with metastatic well-differentiated follicular carcinoma without a primary tumor in the thyroid.

Therapeutic Potential of Lentivirus-Mediated Glucagon-Like Peptide-1 Gene Therapy for Diabetes.

Postprandial glucose-induced insulin secretion from the islets of Langerhans is facilitated by glucagon-like peptide-1 (GLP-1)-a metabolic hormone with insulinotropic properties. Among the variety of effects it mediates, GLP-1 induces delta cell secretion of somatostatin, inhibits alpha cell release of glucagon, reduces gastric emptying, and slows food intake. These events collectively contribute to weight loss over time. During type 2 diabetes (T2DM), however, the incretin response to glucose is reduced and accompanied by a moderate reduction in GLP-1 secretion. To compensate for the reduced incretin effect, a human immunodeficiency virus-based lentiviral vector was generated to deliver DNA encoding human GLP-1 (LentiGLP-1), and the anti-diabetic efficacy of LentiGLP-1 was tested in a high-fat diet/streptozotocin-induced model of T2DM. Therapeutic administration of LentiGLP-1 reduced blood glucose levels in obese diabetic Sprague Dawley rats, along with improving insulin sensitivity and glucose tolerance. Normoglycemia was correlated with increased blood GLP-1 and pancreatic beta cell regeneration in LentiGLP-1-treated rats. Plasma triglyceride levels were also normalized after LentiGLP-1 injection. Collectively, these data suggest the clinical potential of GLP-1 gene transfer therapy for the treatment of T2DM.

Evaluation of Incidental Thyroid Nodules in Cancer Patients.

OBJECTIVE: Frequency of thyroid cancer in incidental thyroid nodules identified by imaging techniques in cancer patients is higher than that in the normal population. In the retrospective study, we have both investigated the incidence of thyroid cancer in incidentally identified nodules and compared the imaging techniques to determine whether there is any difference between them in detection of malign nodules. METHODS: A total of 7319 patients who underwent thyroid fine-needle aspiration biopsy (FNAB) were included in the study. The data of 174 patients who had previously been diagnosed with a hematologic or solid malignancy prior to the FNAB procedure and had incidentally identified thyroid nodules were evaluated retrospectively. RESULTS: Eighty-six (49.5%) of the incidental nodules were identified with ultrasonography (USG), 62 (35.6%) with positron emission tomography (PET) or PET/computed tomography (PET/CT), and 26 (14.9%) with CT. As a result of thyroidectomy, papillary carcinoma was identified in 8 (4.6%) patients, and metastasis to the thyroid of a primary cancer was found in 3 (1.7%) patients. While the papillary carcinoma proportion in the nodules identified by USG was 3.4%, PET/CT was 8.9%. A cut-off maximal standardized uptake value of 11.6 in PET/CT indicated malignancy achieving a sensitivity of 83.3% and a specificity of 91.1%. CONCLUSION: Whether the nodule in the incidental thyroid nodules of cancer patients is identified using USG or PET/CT, the risk of thyroid cancer is similar. However, cancer risk is higher in the event of a higher focal uptake in the nodules identified by PET/CT.

Turkish assessment of SURF (SUrvey of Risk Factor Management) study: Control rates of cardiovascular risk factors derived from databases of 15 different levels of health centers in Turkey.

OBJECTIVE: The aim of this study was to evaluate the adherence to recommendations for secondary prevention and the achievement of treatment targets for the control of risk factors in patients with established coronary heart disease (CHD) who were followed-up at various healthcare facilities in Turkey. METHODS: According to the protocol of the international Survey of Risk Factor Management study, questionnaire forms were completed and demographic, anthropometric, and laboratory data of CHD patients who were followed-up at a total of 15 selected primary, secondary, and tertiary healthcare centers were recorded. RESULTS: Among a total of 724 CHD patients (69.8% male; mean age: 63.3±10.7 years) included in the study, 18.4% were current smokers, only 19.1% had normal body mass index, and 22.1% had waist circumference below the limit of abdominal obesity. Physical activity was insufficient in 53% of the patients, 47.3% had low high-density lipoprotein cholesterol value, 46% had triglyceride level above 150 mg/dL, and 67% had glycated hemoglobin value of 6.5% or above. Of all the patients, 88.1% were using antiplatelet drugs, 71.4% were using beta-blockers, 55.7% were using statins, and 41.9% were using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Blood pressure was under control in 56.7% of the hypertensive patients using antihypertensive drugs, and the proportion of diabetic patients who reached glycemic control targets using antidiabetic drugs was 35.9%. Low-density lipoprotein cholesterol was below 70 mg/dL in 12.2% of the patients using statins. CONCLUSION: According to the data obtained, among Turkish CHD patients, the control rate of cardiovascular risk factors is low, and implementation of the recommendations regarding lifestyle modification and medication use for secondary prevention in the current guidelines are insufficient.

Which type 2 diabetes mellitus patients should be screened for subclinical Cushing's syndrome?

OBJECTIVE: Diabetes or impaired glucose tolerance are common in patients with Cushing's syndrome (CS). In this study we investigated the incidence of subclinical Cushing's syndrome (SCS) in type 2 diabetic patients with poor and good metabolic control and the relationship between blood glucose and cortisol levels. DESIGN: A total of 400 type 2 diabetes mellitus (T2DM) patients (Group A, HbA1c ≥8%, n=250; Group B, HbA1c ≤6.5%, n=150) were included in the study. Biochemical tests followed by the 1 mg dexamethasone suppression test (DST) were performed. If post-DST cortisol levels were above 1.8 µg/dl (non-suppressed group), the 2 mg DST test was performed for 2 days. Among the patients, post-DST cortisol of at least 1.8 µg/dL and midnight serum cortisol levels of at least 7.5 µg/dL confirmed the diagnosis of CS. RESULTS: While SCS was observed in 5 patients (2%) in Group A, no case was observed in group B. There was a statistically significant difference between groups for basal cortisol and post-DST cortisol results (p<0.001 and p<0.001, respectively). Microvascular complication rates were higher in the non-suppressed group (p=0.007). Post-DST cortisol levels had a positive correlation with the number of complications and HbA1c levels (respectively r=0.213, p<0.001, and r=0.191, p<0.001). Multivariate regression analysis revealed that durations of DM, HbA1c level, and post 1 mg DST cortisol levels were associated with the number of complications. CONCLUSIONS: This study shows the presence of SCS in a notable number in T2DM patients having poor metabolic control. Screening with 1 mg and 2 mg DST of T2DM patients with poor metabolic control who are also obese and hypertensive and have microvascular complications may be an appropriate method for detection of SCS.

The effects of hyperventilation on axonal excitability parameters in patients with diabetes mellitus and polyneuropathy.

AIMS: We aimed to explore axonal excitability parameters in patients with diabetes mellitus (DM) and polyneuropathy (PNP) as well as those without PNP. METHODS: We used the short TROND protocol by QTRAC to measure axonal excitability parameters (strength-duration time constant (SDTC), rheobase, etc.) in 12 healthy subjects and 14 DM patients with PNP and 10 DM patients without PNP. The short TROND protocol was performed before and after 20min of deep hyperventilation in healthy subjects and patients with DM. Also, venous blood pH and partial pressure of O2 and CO2 were recorded before hyperventilation (HPV) and after 20min of HPV. A "hyperventilation score" was evaluated before and after HPV. RESULTS: When the values of DM with PNP group and control group before HPV were compared, SDTC and latency were statistically significant. Comparing the values of the excitability parameters after HPV showed statistically significant changes in the SDTC, rheobase, and refractoriness at 2.5ms in controls and DM patients without PNP. HPV resulted in no changes in SDTC in DM patients with PNP. CONCLUSION: The results of this study suggest that patients with DM and healthy subjects have different responses to HPV, and pH changes have different effects on diabetic PNP compared with healthy controls and DM patients without PNP.

Parathyroidectomy in asymptomatic primary hyperparathyroidism reduces carotid intima-media thickness and arterial stiffness.

OBJECTIVE: Although an International Workshop has suggested that cardiovascular assessment in asymptomatic primary hyperparathyroidism (PHPT) patients is not necessary, improvements in risk factors of subclinical atherosclerosis have been shown following parathyroidectomy. The objectives of this study were to determine whether parathyroidectomy in asymptomatic PHPT patients causes any change in carotid intima-media thickness (CIMT), arterial stiffness [pulse wave velocity (PWV)] and soluble CD40 ligand (sCD40L) levels. DESIGN: Prospective study evaluating female patients diagnosed with asymptomatic PHPT in a single centre over a 6-month period. PATIENTS: A total of 48 subjects were included: 17 hypercalcaemic (HC, mean age: 51 ± 8 years, Ca: 2·73 ± 0·17 mmol/l) and 16 normocalcaemic (NC, mean age: 58 ± 7 years, Ca: 2·30 ± 0·10 mmol/l) PHPT patients, and 15 healthy controls (mean age: 52 ± 4 years, Ca: 2·27 ± 0·07 mmol/l). MEASUREMENTS: Biochemical tests, CIMT, PWV and sCD40L levels were compared at baseline and 6 months after parathyroidectomy (PTx). RESULTS: At baseline, CIMT and PWV values in the HC and NC patients were higher than in the control group. While there was a significant reduction in CIMT (601 ± 91 µm vs 541 ± 65 µm, P = 0·006) and PWV (9·6 ± 1·8 vs 8·4 ± 1·5 m/s, P = 0·000) in the hypercalcaemic group at the end of the 6th month after PTx, no change was observed in normocalcaemic group (P = 0·686 and P = 0·196 respectively). No differences were observed in sCD40L levels between patient and control groups or between baseline and 6 months in patients undergoing parathyroidectomy. CONCLUSION: Parathyroidectomy leads to an improvement in the structural and functional impairment associated with atherosclerosis in the vascular wall in asymptomatic hypercalcaemic PHPT patients.

Incretins: their physiology and application in the treatment of diabetes mellitus.

Therapies targeting the action of incretin hormones have been under close scrutiny in recent years. The incretin effect has been defined as postprandial enhancement of insulin secretion by gut-derived factors. Likewise, incretin mimetics and incretin effect amplifiers are the two different incretin-based treatment strategies developed for the treatment of diabetes. Although, incretin mimetics produce effects very similar to those of natural incretin hormones, incretin effect amplifiers act by inhibiting dipeptidyl peptidase-4 (DPP-4) enzyme to increase plasma concentration of incretins and their biologic effects. Because glucagon-like peptide-1 (GLP-1) is an incretin hormone with various anti-diabetic actions including stimulation of glucose-induced insulin secretion, inhibition of glucagon secretion, hepatic glucose production and gastric emptying, it has been evaluated as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM). GLP-1 also manifests trophic effects on pancreas such as pancreatic beta cell growth and differentiation. Because DPP-4 is the enzyme responsible for the inactivation of GLP-1, DPP-4 inhibition represents another potential strategy to increase plasma concentration of GLP-1 to enhance the incretin effect. Thus, anti-diabetic properties of these two classes of drugs have stimulated substantial clinical interest in the potential of incretin-based therapeutic agents as a means to control glucose homeostasis in T2DM patients. Despite this fact, clinical use of GLP-1 mimetics and DPP-4 inhibitors have raised substantial concerns owing to possible side effects of the treatments involving increased risk for pancreatitis, and C-cell adenoma/carcinoma. Thus, controversial issues in incretin-based therapies under development are reviewed and discussed in this manuscript.