Search Results
Search for other papers by Jana Ernst in
Google Scholar
PubMed
Search for other papers by Katharina Gert in
Google Scholar
PubMed
Search for other papers by Frank Bernhard Kraus in
Google Scholar
PubMed
Search for other papers by Ulrike Elisabeth Rolle-Kampczyk in
Google Scholar
PubMed
Search for other papers by Martin Wabitsch in
Google Scholar
PubMed
Search for other papers by Faramarz Dehghani in
Google Scholar
PubMed
Search for other papers by Kristina Schaedlich in
Google Scholar
PubMed
The rapid increase of obesity during the last decades and its future prospects are alarming. Besides the general discussed causes of obesity, the ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis received more attention in recent years. This hypothesis postulates an adverse influence during early development that programs the unborn child for metabolic dysfunctions later in life. Childhood obesity – an as much increasing problem – can be predisposed by maternal overweight and diabetes. Both, obesity and hyperinsulinemia are major causes of female hyperandrogenemia. As predicted by the DOHaD hypothesis and shown in animal models, developmental androgen excess can lead to metabolic abnormalities in offspring. In this study, we investigated, if androgen exposure adversely affects the adipogenic differentiation of preadipocytes and the endocrine function of adult adipocytes. The human SGBS preadipocyte model was used to affirm the de novo biosynthesis of steroid hormones under normal adipogenesis conditions. Normal adipogenesis was paralleled by an increase of corticosteroids and androgens, whereas estrogen remained at a steady level. Treatment with androstenedione had no effect on SGBS proliferation and differentiation, but adult adipocytes exhibited a significant higher accumulation of triglycerides. Progesterone (up to 2-fold), testosterone (up to 38-fold) and cortisone (up to 1.4-fold) – but not cortisol – were elevated by androstenedione administration in adult adipocytes. Estrogen was not altered. Data suggest that androgen does not negatively influence adipogenic differentiation, but steroidogenic function of SGBS adipocytes.
Search for other papers by Clemens Kamrath in
Google Scholar
PubMed
Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany
Search for other papers by Alexander Eckert in
Google Scholar
PubMed
Search for other papers by Birgit Rami-Merhar in
Google Scholar
PubMed
Search for other papers by Sebastian Kummer in
Google Scholar
PubMed
Search for other papers by Martin Wabitsch in
Google Scholar
PubMed
Search for other papers by Katharina Laubner in
Google Scholar
PubMed
Search for other papers by Florian Kopp in
Google Scholar
PubMed
Search for other papers by Silvia Müther in
Google Scholar
PubMed
Search for other papers by Steffen Mühldorfer in
Google Scholar
PubMed
Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany
Search for other papers by Reinhard W Holl in
Google Scholar
PubMed
Objective
To investigate the frequency, treatment, and outcome of patients with diabetes due to severe insulin resistance syndromes (SIRS).
Research Design and Methods
Based on data from the multicenter prospective Diabetes Registry DPV, we analyzed diagnosis, treatment, and outcome of 636,777 patients with diabetes from 1995 to 2022.
Results
Diabetes due to SIRS was documented in 67 cases (62.7% females), 25 (37%) had lipodystrophies (LD) and 42 (63%) had congenital defects of insulin signaling. The relative frequency compared to type 1 diabetes (T1D) was about 1:2300. Median age at diabetes diagnosis in patients with SIRS was 14.8 years (interquartile range (IQR) 12.8–33.8).
A total of 38 patients with SIRS (57%) received insulin and 34 (51%) other antidiabetics, mostly metformin. As high as 16% of patients with LD were treated with fibrates. Three out of eight patients with generalized LD (37.5%) were treated with metreleptin and one patient with Rabson–Mendenhall syndrome was treated with recombinant insulin-like growth factor 1.
The median glycated hemoglobin level at follow-up was 7.1% (54 mmol/mol). Patients with LD had higher triglycerides than patients with T1D and T2D (P < 0.001 and P = 0.022, respectively), and also significantly higher liver enzymes and lower high-density lipoprotein cholesterol than patients with T1D (P < 0.001).
Patients with insulin receptor disorders were significantly less likely to be treated with antihypertensive medication than patients with T2D (P = 0.042), despite having similar levels of hypertension.
Conclusions
Diabetes due to SIRS is rarely diagnosed and should be suspected in lean children or young adults without classical T1D. Awareness of cardiovascular risk factors in these patients should be raised.
