Metformin Improves the Hepatic Steatosis Index in Non-Obese Patients with Polycystic Ovary Syndrome.

Non-alcoholic fatty liver disease (NAFLD) is a common yet little recognized health problem in women with polycystic ovary syndrome (PCOS). In a retrospective setting, we investigated the effects of metformin treatment on the hepatic steatosis index (HSI) as a readily available biomarker panel for NAFLD. HSI values of >36 are considered to be highly suggestive for NAFLD. In our cohort, HSI values indicating NAFLD were found in 60/81 (74.1%) women at baseline. The mean HSI improved significantly after the metformin treatment from 43.2 ± 1.0 to 41.0 ± 1.1. Subgroup analyses of non-obese (body mass index (BMI) < 30 kg/m2), obese (BMI 30−35 kg/m2) and very obese (BMI > 35 kg/m2) women yielded mean baseline HSI values of 35.5 ± 4.5, 41.2 ± 2.7 and 51.2 ± 4.7, respectively. A significant improvement in the HSI of 1.5 ± 2.1 was observed after metformin treatment in non-obese women but not in the obese subgroups. The data suggest a new aspect of metformin treatment in non-obese PCOS patients, namely, a possible improvement in NAFLD. This study highlighted hepatic steatosis as a common comorbidity in PCOS patients that can severely affect their long-term health, and therefore, deserves more attention in the management of PCOS patients.

Influence of the Size of the Foveal Avascular Zone on Functional and Morphological Parameters in Patients with Early-Stage Diabetic Retinopathy.

Purpose: To correlate functional and morphological parameters with foveal avascular zone's (FAZ) size in diabetic patients with mild to moderate stage nonproliferative diabetic retinopathy. Methods: Monocentric and prospective study of a consecutive case series of diabetic patients. Medical history, best corrected visual acuity (BCVA), best corrected high/low contrast visual acuity (BChcVA/BClcVA), mean sensitivity (MS) and mean defect (MD) in central visual field testing, and FAZ size in fluorescein-angiography (FAG) were recorded. Macular thickness (central point thickness CPT, central subfield thickness CST) and volume measurements (central subfield volume CSV, total macular volume) were taken from SD-OCT (6x6mm ETDRS-grid). Groups were categorised as presenting FAZ sizes smaller (G1) or larger (G2) than 0.35mm2. Smallest (Q1) and largest quartiles (Q3) were also compared. Results: Thirty-six of 40 patients were included. MS differed significantly between G1 (n = 6) and G2 (n = 30), and BChcVA/BClcVA as well as TMV correlated significantly with FAZ size in correlation analysis. Mean HbA1c tended to be lower in G1 than G2. Patients in G1 were slightly older than in G2. Treatment period with insulin was shorter in G1/Q1 than in G2/Q3. CPT and TMV were lower in G1/Q1 than in G2/Q3. Our analysis of the FAZ in terms of patient age, HbA1c, disease duration and insulin therapy duration revealed no significance. That lack of significance also applies to BCVA, MS, MD, CPT, CST and CSV. Conclusion: As significantly associated, contrast sensitivity, central visual field parameters and potentially retinal thickness or volume seem to be suitable to detect early macular ischaemia. However, we failed to establish any correlation between FAZ and BCVA.

[Primary hyperparathyreoidism - diagnostic procedures and management]. / Primärer Hyperparathyreoidismus ­ Diagnostik und Therapie.

Hypercalcemia as a laboratory result is often diagnosed during evaluation for osteoporosis. Any form of hypercalcemia should be evaluated further. Owing to fluctuating calcium levels, the measurement should be repeated and corrected for elevated albumin levels by calculation or by measuring ionized calcium. In the diagnosis of primary hyperparathyroidism, measurement of parathyroid hormone, creatinine/glomerular filtration rate, phosphate, 25-OH vitamin D3 and 24-hour urine values are essential for differential diagnosis. Kidney ultrasound is used to detect nephrocalcinosis or kidney stones, and dual-energy X-ray absorptiometry (DXA) to determine bone mineral density (BMD) at the lumbar spine, femoral neck, total femur, and distal forearm. Complete cure is only possible through surgical resection of the adenoma(s). The indication for surgery is dependent on the age of the patient, existing complications, and the patient's preference. Diagnostic imaging should only be performed if surgery is planned. Typically, neck ultrasound and 99mTc MIBI scintigraphy are sufficient to localize the parathyroid adenoma. Presurgical diagnostic evaluation of the thyroid is reasonable for surgical planning. Vitamin-D deficiency should be normalized before surgery. Postsurgical calcium and vitamin-D administration will prevent postsurgical hypocalcemia and hungry-bone disease, and may optimize the outcome of BMD. Treatment of osteoporosis without fractures might not be necessary, owing to normalization of BMD several years after parathyroid surgery. The continuation of specific anti-osteoporotic treatment with bisphosphonates post-surgery did not have any advantage and hence cannot be recommended.

[Asymptomatic primary hyperparathyroidism : Operation or observation?] / Asymptomatischer primärer Hyperparathyreoidismus : Operieren oder beobachten?

BACKGROUND: In many cases primary hyperparathyroidism (PHPT) remains asymptomatic for years and is only detected by abnormalities in routine diagnostics. While symptomatic disease almost always requires surgical treatment, in symptom-free patients the question of whether and in what form treatment should be carried out is particularly important. OBJECTIVE: The aim of this review is to summarize the current recommendations regarding the diagnostics and treatment of asymptomatic PHPT, taking the existing evidence into account. RESULTS AND CONCLUSION: The diagnostics of asymptomatic PHPT is the same as for symptomatic disease. The diagnosis is made in the presence of elevated parathyroid hormone and balanced vitamin D levels when a combination of hypercalcemia, hypophosphatemia and hypercalciuria is present. Borderline laboratory findings occur especially in asymptomatic PHPT and the differential diagnosis of familial hypocalciuric hypercalcemia must be considered. Once the diagnosis is made sonography, radiography or computed tomography (CT) is used to search for nephrolithiasis or nephrocalcinosis. Regarding bone mineral density (BMD) measurements, in addition to routine measurements at the lumbar spine and femur, measurement at the distal radius is important as it is the most sensitive site for detecting osteoporosis in PHPT. An indication for parathyroidectomy is confirmed in the case of hypercalcemia > 1.0 mg/dl (>0.25 mmol/l) above the upper limit of normal, hypercalciuria > 400 mg/day (>10 mmol/day), renal insufficiency, proven osteoporosis or age < 50 years. If none of these criteria are fulfilled and surgery is not desired by the patient, annual laboratory check-ups and assessment of BMD every 1-2 years are recommended.

Endoscopic intragastric balloon: a gimmick or a viable option for obesity?

Worldwide, the prevalence of obesity has doubled since 1980 in 70 countries. More than one in three adults now suffer from overweight or obesity. Health problems related to obesity include orthopedic problems, psychiatric conditions, metabolic and cardiovascular diseases, and of increasing concern, cancer. Thus, obesity has an enormous impact on the individual's wellbeing as well as on society's workforce and health care expenses. Medical efforts are ongoing to find safe and effective treatment options for obesity and its metabolic implications. At present, available treatment options include lifestyle interventions, pharmacotherapy, endoscopic applications, and bariatric surgery. Within the range of endoscopic treatment options, the intragastric balloon is the most widely used device. The idea is simple: the gastric volume is reduced by a balloon that is in most cases implanted by an endoscopic procedure similar to a gastroscopy. During the past decades, different models have been developed, which we will briefly introduce in this review. We aim at reviewing the pathophysiology underlying the effect of endoscopic intragastric balloon on weight loss and metabolic changes. We will assess expected short-term and long-term benefits for the patient, and we will discuss common side effects as well as rare complications. We will compare endoscopic intragastric balloon to conservative treatment options with or without pharmacological support on the one hand and to the spectrum of bariatric surgery on the other hand. In most patients, obesity must be considered a chronic disease that requires a lifelong treatment concept. In view of current treatment options for obesity, we will discuss whether endoscopic intragastric balloon is a viable treatment option, and who may be the right patient to benefit from it.

Risk factors for decline in renal function among young adults with type 1 diabetes.

AIMS: To investigate risk factors for declining renal function among subjects with type-1-diabetes. METHODS: Observational study based on data from the diabetes registry DPV. 4424 type-1-diabetes subjects aged ≥18 years, age at onset <18 years were identified. Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (eGFR). Annual rate of renal decline was estimated for each patient using hierarchic linear regression models. Additional regression models were fitted to adjust for covariates. RESULTS: Median age was 26 [Q1; Q3: 21; 39] years. Annual decline of renal function was -1.22 (95% CI: -1.50; -0.94) ml/min/1.73 m2. At baseline, higher eGFR was related to more rapid decline compared to impaired or reduced eGFR (GFR ≥ 90: -2.06 (-2.35; -1.76), 60 ≤ GFR < 90: 0.45 (0.08; 0.81), GFR < 60: 0.52 (-0.24; 1.29) ml/min/1.73 m2, p < 0.01). During follow-up, the highest decline was associated with reduced renal function, whereas the lowest decline was related to normal kidney function (p < 0.01). Poor metabolic control (p = 0.04), hypertension (p < 0.01) and albuminuria (p = 0.03) were associated with more rapid loss of kidney function. No difference was observed among insulin regimen. CONCLUSION: Among this large type-1-diabetes cohort, more rapid loss of kidney function was related to higher baseline eGFR, log-term worse metabolic control and diabetic comorbidities.

Polycystic Ovary Syndrome (PCOS) in Juvenile and Adult Type 1 Diabetes in a German/Austrian Cohort.

Context While an association between PCOS and type 2 diabetes is well established, to date there have been few data on clinical care of type 1 diabetes (T1D) patients with PCOS. Objective The aim of our study was to characterize T1D patients with the comorbidity of PCOS within the DPV cohort with regard to diabetes phenotype, therapy and metabolic control. Design and Setting Clinical data from the prospective German/Austrian DPV cohort on patients with T1D and documented PCOS (n=76) were compared to female T1D controls (n=32,566) in reproductive age. Results The age at T1D manifestation in PCOS patients was later than in the control group (14.9±8.2 vs. 11.8±7.0 years, p<0.001). PCOS patients had higher BMI-SDS (0.92±0.11 vs. 0.38±0.01, p<0.001), metformin and oral contraceptives were used more frequently (p<0.001). A1c levels were significantly lower (7.92 +/- 0.23% vs. 8.43±0.01%, p<0.05) despite of lower insulin requirements (0.76±0.04 IU/kg/d vs. 0.84±0.00 IU/kg/d, p<0.05). In the PCOS group, higher rates of dyslipidemia (63.4 vs. 48.7%, p =0.032) and thyroid disorders (42.2% vs. 21.2%, p<0.001) were present. Discussion While patients with T1D and comorbid PCOS showed features of a "type 1.5 diabetes" phenotype, insulin requirements per kg body weight were not higher and metabolic control was better, which could be explained only partially by additional metformin therapy. A more precise genetic and metabolic characterisation of these patients is needed to answer open questions on the underlying autoimmune process and residual ß-cell function.

Real-life experience of patients starting insulin degludec. A multicenter analysis of 1064 subjects from the German/Austrian DPV registry.

BACKGROUND: The long-acting insulin analogue degludec is a therapeutic option for patients with type 1 (T1D) or type 2 diabetes (T2D). Aim of this analysis was to investigate differences in clinical characteristics of patients before and after initiating degludec use in a cohort of German/Austrian patients. METHODS: 1064 subjects with T1D/T2D and documented degludec use from the Diabetes-Patient-Follow-Up (DPV) registry were included. The follow-up cohort (n=421) comprised patients with available data before and 3-15months after switching to degludec. A t-test for paired values was implemented to compare rates of severe hypoglycaemia, and mean values for HbA1C, BMI, basal insulin dose/kg bodyweight/day, and the number of basal insulin injections/day before and after switching to degludec Results were stratified by type of diabetes. In T1D, subgroup analyses were conducted (age, sex, basal insulin used before switching). P<0.05 was considered significant. FINDINGS: In T1D (n=360), basal insulin dose (0.43±0.17 to 0.38±0.13IU) and the number of basal injections/day (1.7±0.6 to 1.1±0.3) decreased whereas BMI increased from 23.2±4.8 to 24.0±5.0kg/m2 (all p<0.0001) after switching to degludec. No significant changes were observed regarding rates of severe hypoglycaemia or HbA1C-values. Findings were comparable for subgroups. In T2D (n=61), basal insulin dose (0.41±0.23 to 0.38±0.21; p=0.1730) and the number of basal injections/day (1.3±0.4 to 1.1±0.3; p=0.0097) decreased after switching to degludec. HbA1C improved from 7.9±1.6 to 7.1±1.5% (p<0.0001). CONCLUSIONS: The DPV registry provides data from real-life diabetes care. Our analysis predominantly confirmed results from clinical trials and provides additional information complementing the clinical study program of degludec.

Exercise training-induced adaptations associated with increases in skeletal muscle glycogen content.

Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism leading to increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4 or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. As compared with sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase (GSK)-3. Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of R(GL)(G(M)), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1 activity, GSK-3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~ 40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks, and may function as a negative feedback mechanism in response to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms, including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase, and PP1 activity.

Effects of exercise training on subcutaneous and visceral adipose tissue in normal- and high-fat diet-fed rats.

Regular physical activity improves glucose tolerance and decreases adiposity. Our aim was to investigate the effects of exercise training on subcutaneous (inguinal) and visceral (parametrial) adipose tissue in rats that were fed a chow diet (13% fat) or made insulin resistant by a high-fat diet (60% fat). Sprague-Dawley rats performed 4 wk of voluntary wheel running or were kept as sedentary controls. The training groups fed chow and the high-fat diet achieved similar running distances (8.8 +/- 1.8 and 9.3 +/- 1.9 km/day, respectively). Training improved oral glucose tolerance in chow-fed rats and prevented the glucose intolerance that occurred in sedentary rats fed the high-fat diet. In both subcutaneous and visceral adipose tissue, the high-fat diet-induced increases in fat pad weight (67% and 133%, respectively), adipocyte size (20% and 43%), and cell number (36% and 65%) were completely prevented by exercise training. Cytokine mRNA expression in visceral fat did not change with exercise training. However, in subcutaneous fat, training actually increased mRNA expression of several cytokines [IL-6: 80% (P < 0.05); TNF-alpha: 100% (P < 0.05); IL-1 receptor antagonist (IL-1Ra): 57% (P = 0.08)] with no detectable increases in serum cytokine concentrations. In summary, exercise training can overcome high-fat diet-induced impairments in glucose tolerance and increases in adipocyte size, cell number, and fat pad mass. Improved glucose tolerance was accompanied by an increase in cytokine gene expression in subcutaneous fat. This finding raises the possibility of a specific role of subcutaneous adipose tissue in adaptive responses to exercise training.