Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.

AIM: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up. METHODS: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months. RESULTS: The Kaplan-Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan-Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan-Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan-Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. CONCLUSIONS: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.

Weight management strategies for patients with PCOS: current perspectives.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women. Overweight and obesity commonly accompany the syndrome at the clinic and are significant concerns for women with PCOS. AREAS COVERED: Herein, we provide an overview of the relevant literature on weight management strategies in women with PCOS. We performed an electronic-based search using PubMed until February 2021. We aimed to summarize available evidence of different weight-reducing interventions in PCOS and outline the gaps in our current knowledge and recommend areas for further research. EXPERT OPINION: PCOS is closely linked to obesity and increased adiposity enhances severity and expression of PCOS phenotype. Current data suggest that weight loss is associated with improved metabolic, endocrine, reproductive, cardiovascular and psychological features in overweight and obese women with PCOS. Lifestyle interventions including diet and exercise, anti-obesity medications and bariatric surgery have been used as therapeutic approaches for short-term management of obesity in PCOS with varying success rates. Large and sufficiently powered studies are required in order to determine long-term effects of weight management strategies and potential benefits beyond weight loss in the syndrome. This would allow informing the guidelines to make PCOS specific evidence-based recommendations.

Polycystic Ovary Syndrome and Brain: An Update on Structural and Functional Studies.

CONTEXT: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women in reproductive age and is associated with reproductive, endocrine, metabolic, cardiovascular, and psychological outcomes. All these disorders are thought to be affected by central mechanisms which could be a major contributor in pathogenesis of PCOS. EVIDENCE ACQUISITION: This mini-review discusses the relevance of central nervous system imaging modalities in understanding the neuroendocrine origins of PCOS as well as their relevance to understanding its comorbidities. EVIDENCE SYNTHESIS: Current data suggest that central nervous system plays a key role in development of PCOS. Decreased global and regional brain volumes and altered white matter microstructure in women with PCOS is shown by structural imaging modalities. Functional studies show diminished reward response in corticolimbic areas, brain glucose hypometabolism, and greater opioid receptor availability in reward-related regions in insulin-resistant patients with PCOS. These structural and functional disturbances are associated with nonhomeostatic eating, diminished appetitive responses, as well as cognitive dysfunction and mood disorders in women with PCOS. CONCLUSION: Structural and functional brain imaging is an emerging modality in understanding pathophysiology of metabolic disorders such as diabetes and obesity as well as PCOS. Neuroimaging can help researchers and clinicians for better understanding the pathophysiology of PCOS and related comorbidities as well as better phenotyping PCOS.

Magnetic resonance spectroscopy to assess hepatic steatosis in patients with lipodystrophy.

BACKGROUND/AIMS: Lipodystrophy is a rare metabolic disorder characterized by near total or partial lack of subcutaneous adipose tissue and associated with insulin resistance. We aimed to evaluate the efficacy of magnetic resonance spectroscopy imaging (MRS) to explore the fat content of the liver in patients with lipodystrophy and to determine the relationship between the liver fat accumulation and clinical presentations of lipodystrophy. MATERIALS AND METHODS: Between July 2014 and February 2016, 34 patients with lipodystrophy were assessed by MRS for quantification of hepatic steatosis. All patients had metabolic abnormalities associated with insulin resistance. Metabolic parameters and the MRS findings were analyzed to identify potential correlations between the liver fat content and disease severity. RESULTS: The MRS fat ratios (MRS-FR) were markedly higher, indicating severe hepatic steatosis in lipodystrophy. Patients with generalized and partial lipodystrophy had comparable levels of MRS-FRs, although patients with generalized lipodystrophy were significantly younger. Patients with genetically based lipodystrophy had elevated MRS-FR compared to those with acquired lipodystrophy (p=0.042). The MRS-FR was positively correlated with liver enzyme alanine aminotransferase (p=0.028) and serum adiponectin (p=0.043). CONCLUSION: Our data suggest that MRS might be an effective, noninvasive imaging method to quantify hepatic fat content in patients with lipodystrophy. Further studies are needed to validate the technique and threshold values which would allow accurate comparison of data acquired by different machines and centers.

Validity and reliability of the Turkish version of the Michigan Neuropathy Screening Instrument

Background/aim: The aim of this study was to demonstrate the validity and reliability of the Turkish version of the Michigan Neuropathy Screening Instrument (MNSI-TR). Materials and methods: The study included 127 patients aged 45­76 years who were previously diagnosed with type 1 or 2 diabetes. Stability of the instrument was assessed by intraclass correlation coefficient. Reliability of the MNSI-TR was assessed using the Kuder­ Richardson formula 20 test, item-total correlations, and floor/ceiling effect. Validity was evaluated with receiver operating characteristic curve analysis. A logistic regression model was used to determine to what degree the MNSI-TR explain nerve conduction study (NCS) results in the prediction of neuropathy. Results: With a cut-off value of 3.5 for the questionnaire, sensitivity and specificity of the MNSI-TR were 75.5% and 68.1%, respectively. A cut-off of 2.75 for the physical assessment part of the scale resulted in 87.5% sensitivity and 93.6% specificity. The scale was able to diagnose neuropathy in the rate of 71.5% of the patients diagnosed with neuropathy by NCS. Conclusion: The MNSI-TR is a valid and reliable method for evaluating diabetic peripheral neuropathy in Turkish speaking societies. It must be obtained a minimum of 4 points from the questionnaire part and a minimum of 2.5 points from the physical assessment part for the diagnosis of neuropathy

Impact of Obesity on the Metabolic Control of Type 2 Diabetes: Results of the Turkish Nationwide Survey of Glycemic and Other Metabolic Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study).

BACKGROUND: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro- and microvascular complications of patients are not apparent. OBJECTIVES: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. METHODS: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. RESULTS: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. CONCLUSION: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity.

A subset of patients with acquired partial lipodystrophy developing severe metabolic abnormalities.

Purpose/Aim of the study: Acquired partial lipodystrophy (APL) is a rare disease characterized by selective loss of adipose tissue. In this study, we aimed to present a subset of patients with APL, who developed severe metabolic abnormalities, from our national lipodystrophy registry. MATERIALS AND METHODS: Severe metabolic abnormalities were defined as: poorly controlled diabetes (HbA1c above 7% despite treatment with insulin more than 1 unit/kg/day combined with oral antidiabetics), severe hypertriglyceridemia (triglycerides above 500 mg/dL despite treatment with lipid-lowering drugs), episodes of acute pancreatitis, or severe hepatic involvement (biopsy-proven non-alcoholic steatohepatitis (NASH)). RESULTS: Among 140 patients with all forms of lipodystrophy (28 with APL), we identified 6 APL patients with severe metabolic abnormalities. The geometric mean for age was 37 years (range: 27-50 years; 4 females and 2 males). Five patients had poorly controlled diabetes despite treatment with high-dose insulin combined with oral antidiabetics. Severe hypertriglyceridemia developed in five patients, of those three experienced episodes of acute pancreatitis. Although all six patients had hepatic steatosis at various levels on imaging studies, NASH was proven in two patients on liver biopsy. Our data suggested that APL patients with severe metabolic abnormalities had a more advanced fat loss and longer disease duration. CONCLUSIONS: We suggest that these patients represent a potential subgroup of APL who may benefit from metreleptin or investigational therapies as standard treatment strategies fail to achieve a good metabolic control.

Does the ACR TI-RADS scoring allow us to safely avoid unnecessary thyroid biopsy? single center analysis in a large cohort.

INTRODUCTION: The American College of Radiology (ACR) has recently proposed a guideline that recommends clinicians to perform thyroid fine-needle aspiration biopsy (FNAB) on the basis of ultrasound features. In this study, we focused on nodules for which no biopsy is recommended by the ACR Thyroid Imaging, Reporting and Data System (TI-RADS) guideline. SUBJECTS AND METHODS: Two-thousand eight-hundred and forty-seven consecutive patients with thyroid nodules who underwent FNAB according to the 2009 American Thyroid Association (ATA) guideline were included. The nodules were re-classified according to the ACR TI-RADS guideline as benign (TR1), not suspicious (TR2), mildly suspicious (TR3), moderately suspicious (TR4) and highly suspicious (TR5). The TR3 category was stratified into two subcategories as regard to the nodule size (TR3; <25 mm and TR3; ≥25 mm). RESULTS: Two-hundred and thirty-three (8.2%) patients with non-diagnostic FNABs were excluded. When the TR2 and TR3; <25 mm categories were merged, FNAB was suggestive of thyroid cancer in 17 of 1382 patients (1.2%). FNAB revealed Bethesda IV-VI in 5 of 273 patients with the TR3; ≥25 mm category (1.8%), in 61 of 896 patients with the TR4 category (6.8%), and in 18 of 63 of patients with the TR5 category (28.6%). The ACR TI-RADS scoring was 98.8% (95% CI: 98 to 99.3) specific for identification of a benign nodule. CONCLUSION: Our data suggest that ACR TI-RADS scoring is an applicable and potentially cost-effective approach to determine thyroid nodules to be biopsied, although a small proportion of thyroid cancers would be missed.

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

OBJECTIVES: Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. STUDY DESIGN: In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. METHODS: Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. RESULTS: Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CONCLUSIONS: CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease.

Chemical shift magnetic resonance imaging could predict subclinical cortisol production from an incidentally discovered adrenal mass.

CONTEXT: To investigate whether any association between chemical shift magnetic resonance (MRI) findings, cortisol secretion and pathological findings exists that could predict subclinical hypercortisolism (SCH) in patients with adrenal incidentalomas (AI). DESIGN: Retrospective, cross-sectional study in a tertiary centre. PATIENTS: Sixty-eight subjects with AIs and 13 patients with Cushing's syndrome (CS). Patients with AIs were categorized according to cortisol levels post 1 mg dexamethasone (post-DST). MEASUREMENTS: Visual inspection of the lipid content of the adrenal tumour and calculation of adrenal-to-spleen ratio (ASR), the signal intensity index (SII), volume and the assessment of the association between pathological, radiological and hormonal findings in surgically treated patients. RESULTS: Percentage of clear cells was correlated with ASR (r = -.525, P = .01), SII (r = .465, P = .025), post-DST cortisol (r = -.711, P < .001) and ACTH (r = .475, P = .046). By ANOVA and post hoc analysis, patients with CS and five subjects with a post-DST cortisol greater than 137 nmol/L differed significantly in ASR and SII from those with a post-DST cortisol less than 50 nmol/L. An ASR level higher than 0.245 (OR 19.7, 95% CI 1.5-257.5; P = .023) and a SII level lower than 78.37 (OR 15.6, 95% CI 1.2-20; P = .034) remained as the independent predictors for SCH while age, presence of arterial hypertension or tumour volume did not make significant contribution to the models. CONCLUSIONS: Cortisol hypersecretion by adrenal adenomas is associated with distinctive MRI characteristics. The quantitative assessment of intracellular lipid in an AI could help distinguish patients with a clear phenotype of SCH.

The Effect of Retraining on Treatment Success, Quality of Life, and Metabolic Parameters in Patients with Type 1 Diabetes Using an Insulin Pump.

OBJECTIVE: To investigate the effect of insulin pump user retraining on treatment success, quality of life, and metabolic parameters of patients with type 1 diabetes using continuous subcutaneous insulin infusion. SUBJECTS AND METHODS: A total of 35 subjects participated in this prospective study. All patients were given insulin pump user retraining. Their knowledge level and application skills, metabolic parameters, quality of life, and satisfaction from treatment were evaluated at baseline and after 6 months. RESULTS: There was significant improvement in patients' knowledge and application skills after insulin pump user retraining (self-assessment of user skills: 69.7 ± 11.5 vs. 76.3 ± 11.3, p < 0.001; knowledge level on technical issues: 3.3 ± 1.1 vs. 4.1 ± 1.8, p = 0.003; glucose monitoring: 27.1 ± 5.8 vs. 29.2 ± 5.6, p = 0.006; management of hyperglycemia: 13.1 ± 3.2 vs. 15.7 ± 3.4, p < 0.001; management of pump and infusion site problems: 8.8 ± 2.6 vs. 10.6 ± 2.6, p = 0.001). Hemoglobin (Hb)A1c levels of patients with poor glycemic control improved after retraining (8.61% ± 0.78 vs. 8.23% ± 0.79, p = 0.02). However, no significant improvement in quality of life and treatment satisfaction parameters were found. CONCLUSION: Management of type 1 diabetes in insulin pump users can be significantly improved by retraining. Even a basic short-term retraining program helps patients to increase their knowledge level and ability to more effectively use the insulin pump. The fact that retraining significantly improves glycemic parameters in patients with poor metabolic control indicates that priority should be given to this group of patients. Further studies with individualized training programs in larger sample sizes with long-term follow-up are needed to establish the importance of retraining and create re-education plans for patients with type 1 diabetes using an insulin pump.

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

PURPOSE: To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. METHODS: Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. RESULTS: Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. CONCLUSION: This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.