Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women, with a wide spectrum of possible phenotypes, symptoms and sequelae according to the current clinical definition. However, there are women who do not fulfill at least two out of the three commonly used “Rotterdam criteria” and their risk of developing type 2 diabetes or obesity later in life is not defined. Therefore, we addressed this important gap by conducting a retrospective analysis based on 750 women with and without PCOS. We compared four different PCOS phenotypes according to the Rotterdam criteria with women who exhibit only one Rotterdam criterion and with healthy controls. Hormone and metabolic differences were assessed by analysis of variance (ANOVA) as well as logistic regression analysis. We found that hyperandrogenic women have per se a higher risk of developing insulin resistance compared to phenotypes without hyperandrogenism and healthy controls. In addition, hyperandrogenemia is associated with developing insulin resistance also in women with no other Rotterdam criterion. Our study encourages further diagnostic and therapeutic approaches for PCOS phenotypes in order to account for varying risks of developing metabolic diseases. Finally, women with hyperandrogenism as the only symptom should also be screened for insulin resistance to avoid later metabolic risks.

25-hydroxyvitamin D (25(OH)D) is commonly measured to assess vitamin D status. Other vitamin D metabolites such as 24,25-dihydroxyvitamin D (24,25(OH)₂D) provide additional insights into vitamin D status or metabolism. Earlier studies suggested that the vitamin D metabolite ratio (VMR), calculated as 24,25(OH)₂D/25(OH)D, could predict the 25(OH)D increase after vitamin D supplementation. However, the evidence for this additional value is inconclusive. Therefore, our aim was to assess whether the increase in 25(OH)D after supplementation was predicted by the VMR better than baseline 25(OH)D. Plasma samples of 106 individuals (25(OH)D < 75 nmol/L) with hypertension who completed the Styrian Vitamin D Hypertension Trial (NC.T.02136771) were analyzed. Participants received vitamin D (2800 IU daily) or placebo for 8 weeks. The treatment effect (ANCOVA) for 25(OH)D₃, 24,25(OH)₂D₃ and the VMR was 32 nmol/L, 3.3 nmol/L and 0.015 (all p < 0.001), respectively. Baseline 25(OH)D₃ and 24,25(OH)₂D₃ predicted the change in 25(OH)D₃ with comparable strength and magnitude. Correlation and regression analysis showed that the VMR did not predict the change in 25(OH)D₃. Therefore, our data do not support routine measurement of 24,25(OH)₂D₃ in order to individually optimize the dosage of vitamin D supplementation. Our data also suggest that activity of 24-hydroxylase increases after vitamin D supplementation.

Zusammenfassung: Das polyzystische Ovar-Syndrom (PCOS) ist die häufigste Endokrinopathie bei Frauen im gebärfähigen Alter. In den letzten Jahren gab es zahlreiche Fortschritte im Verständnis zu Definition, Pathogenese und Behandlungsmöglichkeiten. Diese Übersichtsarbeit gibt Einblick in diese Erkenntnisse und erläutert mögliche neue Therapiezweige anhand der aktuellen Literatur.Die Symptome des PCOS sind vielfältig und ihre Ausprägung entlang eines breiten Spektrums verteilt. Die wichtigsten klinischen Hinweise sind Hirsutismus, Oligo‑/Amenorrhö, Infertilität sowie Insulinresistenz, Übergewicht/Adipositas und die namensgebenden polyzystischen Ovarien. Da es keine ursächliche Therapie für das Syndrom gibt, sollte die symptomatische Behandlung mit der Patientin und ihren Bedürfnissen abgestimmt werden. Die wichtigsten Therapiemöglichkeiten sind Lebensstilinterventionen, Metformin, hormonelle Kontrazeptiva, (hormonelle) Ovulationsinduktoren sowie chirurgische Eingriffe.In den letzten Jahren haben sich mit dem Zusammenhang von Darmmikrobiom, Hormonen und Energiestoffwechsel weitere potenzielle Behandlungsmöglichkeiten aufgetan, deren Einfluss aktuell untersucht wird. Probiotika könnten dabei helfen, hormonelle und metabolische Prozesse zu modifizieren und dadurch PCOS-typische Symptome zu lindern.

Osteoporosis and diabetes mellitus type 2 (T2DM) are frequently coinciding in elderly patients, increasing with age. The disease is associated with a higher fracture risk despite normal to high planar bone mineral density (BMD) as measured by dual energy bone densitometry (DXA) in these individuals. As BMD measurements do not identify T2DM patients at risk for bone fractures, this coincidence has not been recognized for a long time, though higher mortality and the risk of a delayed wound healing have been found in T2DM patients with major fractures. In patients with diabetes mellitus type 1 (T1DM) fracture risk is even higher, with an up to 12-fold risk as compared to patients with normal glucose metabolism. These patients might be affected from early childhood on, with worse fracture outcomes depending on their glucose control. Pathophysiological conditions that might contribute to the increased fracture risk in both T1DM and T2DM include decreased skeletal quality and properties, aggravated by comorbidities such as macro- and microvascular complications, and chronic inflammation, but there are many open questions to resolve. As specific diagnostic approaches are urgently required, several attempts have been made by new imaging technologies, namely trabecular bone score (TBS), high resolution peripheral quantitative computed tomography (HRpQCT), bone biopsies, histomorphometry and microindentation. New biomarkers of diabetoporosity have been addressed. The complex interaction of these new biomarkers is illustrated by several articles within this issue. We report on the current knowledge in pathophysiology, diagnostics and management of bone in diabetes mellitus. Given the increasing numbers of T2DM and osteoporosis patients worldwide—with a current number of about 415 million T2DM patients, a growing community of T1DM patients and about 9 million osteoporotic fractures annually in 200 million women and probably 120 million men—this is in fact an important problem for future health care.

Background Metformin is a widely used and effective agent in type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS). Yet, the mechanisms of action and the occurrence of side effects (e.g. abdominal bloating and pain), are still poorly understood. Since organic cation transporters (OCTs) are responsible for the hepatic and renal transport of metformin, we investigated a series of short nucleotide polymorphisms (SNPs) in the OCT genes in PCOS and in T2DM patient samples from either our PCOS patient registry or the Graz Diabetes Registry for Biomarker Research (GIRO). Methods After DNA isolation from plasma in 181 PCOS samples and 44 T2DM samples followed by a subsequent polymerase chain reaction (PCR) with a combined TaqMan assay, we compared 17 SNPs (rs456598, rs461473, rs3798174, rs7766568, rs316007, rs3798167, rs662301, rs2048327, rs376563, rs622591, rs9295125, rs3798172, rs2197296, rs12208357, rs34059508, rs628031 and rs3777392) from OCT1 and OCT3 transporters. Results Data of the study participants were analyzed according to the presence or absence of documented metformin-induced side effects. The distributions of different genotypes of the rs2197296 locus in the SLC22A1 gene, the rs376563 locus in the SLC22A2 gene and the rs3798167 locus in the SLC22A3 gene were statistically significant between the two groups. The effect was shown by a higher minor allele frequency in the group with documented metformin associated side effects (χ⁽²⁾ = 3.953, P = 0.047, χ⁽²⁾ = 7.342, P = 0.025 and χ⁽²⁾ = 12.251, P = 0.002 respectively). Conclusion In conclusion, we found three specific allelic variants in OCT candidate genes with distinct associations for side effects in metformin users either in PCOS or in T2DM. Therefore, those variants can be further investigated to better understand the metformin-associated side effects.

Ein Erratum zu dieser Publikation wurde veröffentlicht: 10.1007/s41969-021-00135-y