Prevalence of Obesity-Related Disease in a Danish Population – The Results of an Algorithm-Based Screening Program

Claus B Juhl,1– 4 Else Marie Bladbjerg,3,5 Bibi Gram,3 Torben Knudsen,3,6 Mette Munk Lauridsen,3,6 Niels-Peter Brøchner Nygaard,1,3,7 Nina Drøjdahl Ryg,1,2,4 Lars Skadhauge,3,8 Anna-Marie Bloch Münster3,5 1Department of Endocrinology, University Hospital of Southern Denmark, Esbjerg, Denmark; 2Steno Diabetes Center Odense, University Hospital of Southern Denmark, Odense, Denmark; 3University of Southern Denmark, Department of Regional Health Research, Odense, Denmark; 4OPEN, Open Patient Data Explorative, Odense University Hospital, Odense, Denmark; 5Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark; 6Department of Gastroenterology, University Hospital of Southern Denmark, Esbjerg, Denmark; 7Department of Neurology, University Hospital of Southern Denmark, Esbjerg, Denmark; 8Department of Occupational Medicine, University Hospital of Southern Denmark, Esbjerg, DenmarkCorrespondence: Claus B Juhl, Department of Endocrinology, University Hospital Southern Denmark, Esbjerg, DK-6700, Denmark, Tel +45 6086 7172, Email [email protected]: The prevalence of obesity continues to rise. People with obesity are at increased risk of several diseases. We tested an algorithm-based screening program for people with a BMI above 30 kg/m2 and present data on the prevalence of previously undiagnosed obesity-related diseases.Patients and Methods: Seven hundred and sixty-nine persons with BMI > 30 kg/m2 and age 18– 60 years were screened for diabetes (assessed by glycosylated hemoglobin and oral glucose tolerance test at HbA1c 43– 48 mmol/mol), sleep apnea (screened by questionnaires and assessed by cardiorespiratory monitoring at indication of sleep disorder), liver steatosis or liver fibrosis (assessed by biochemistry and fibroscan) and arterial hypertension (assessed by both office and 24-hour blood pressure measurement). A reference group of people with a BMI of 18.5– 29.9 kg/m2 was established.Results: Of those referred, 73.0% were women. We identified new diabetes in 4.2%, prediabetes in 9.1%, moderate-to-severe sleep apnea in 25.1%, increased liver fat and increased liver stiffness in 68.1% and 17.4%, respectively, and hypertension or masked hypertension in 19.0%. The prevalence of diseases was much higher among men and increased with BMI. Except for hypertension, we found few participants with undiagnosed disease in the reference group.Conclusion: An algorithm-based screening program is feasible and reveals undiagnosed obesity-related disease in a large proportion of the participants. The disproportional referral pattern calls for a tailored approach aiming to include more men with obesity.Trial Registration: Inclusion of the non-obese group was approved by the Scientific Ethics Committee of The Region of Southern Denmark (project identification number: S-20210091), and the study was reported at clinicaltrials.gov (NCT05176132).Plain Language Summary: The number of people with obesity is going up, and they are at a higher risk for various diseases. We tested a screening program for people referred with a BMI over 30 kg/m2 and presented the prevalence of diseases related to obesity. We screened 769 people aged 18 to 60 years with a BMI over 30 kg/m2 for diabetes (biochemistry and glucose tolerance test), sleep apnea (both questionnaires and home monitoring), liver disease (biochemistry and liver scan) and high blood pressure (office and 24-hour readings). We also tested a reference group of people with BMI 18.5-30 kg/m2. Among those screened, 73.0% were women. We found new cases of diabetes in 4.2%, prediabetes in 9.1%, sleep apnea in 25.1%, increased liver fat in 68.1%, increased liver stiffness in 17.4%, and hypertension or masked hypertension in 19.0%. The diseases were more common in men and increased with both higher BMI and age. Except for hypertension, we found few cases in the reference groups. The screening program uncovered undiagnosed obesity-related diseases in a large group of individuals. The uneven distribution of referrals suggests we need a customized approach to include more men with obesity.Keywords: diabetes, pre-diabetes, sleep apnea, metabolic dysfunction-associated steatotic liver disease, hypertensio

The maturation of the acetylcholine system in the dentate gyrus of gerbils (Meriones unguiculatus) is affected by epigenetic factors.

Busche A, Bagorda A, Lehmann K, Neddens J, Teuchert-Noodt G. The maturation of the acetylcholine system in the dentate gyrus of gerbils (Meriones unguiculatus) is affected by epigenetic factors. J Neural Transm. 2006;113(2):113-124.The current study investigated the influence of impoverished rearing (IR) conditions and a single early methamphetamine challenge (MA; 50 mg/kg i.p.) on day 14 on the postnatal maturation of acetylcholinesterase-positive (AChE+) fibres in the hippocampal dentate gyrus (DG) of gerbils (Meriones unguiculatus). The layer-specific densities of histochemically stained AChE+ fibres were quantified in two planes of the left and right DG in young adults (day 90). Compared to enriched reared (ER) animals, the AChE+ fibre densities turned out to be higher in both the septal and the temporal plane of both hemispheres in saline treated IR and MA treated ER gerbils. The temporal plane was slightly more affected than the septal plane. In IR animals, MA treatment selectively diminished the AChE+ fibre densities in the subgranular layer of both left and right temporal DG. In conclusion, the maturation of AChE+ fibres is vulnerable to both rearing conditions and early MA challenge. The results correlate with our previous studies on the dentate cell proliferation rates and the serotonergic innervation, two parameters which are similarly affected by the experimental design. Thus, disturbances of the ACh system may impair the hippocampal plasticity and hippocampus-related cognitive and emotional function

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex

Lysophosphatidic acid (LPA) is an intercellular signaling lipid that regulates multiple cellular functions, acting through specific G-protein coupled receptors (LPA1–6). Our previous studies using viable Malaga variant maLPA1-null mice demonstrated the requirement of the LPA1 receptor for normal proliferation, differentiation, and survival of the neuronal precursors. In the cerebral cortex LPA1 is expressed extensively in differentiating oligodendrocytes, in parallel with myelination. Although exogenous LPA-induced effects have been investigated in myelinating cells, the in vivo contribution of LPA1 to normal myelination remains to be demonstrated. This study identified a relevant in vivo role for LPA1 as a regulator of cortical myelination. Immunochemical analysis in adult maLPA1-null mice demonstrated a reduction in the steady-state levels of the myelin proteins MBP, PLP/DM20, and CNPase in the cerebral cortex. The myelin defects were confirmed using magnetic resonance spectroscopy and electron microscopy. Stereological analysis limited the defects to adult differentiating oligodendrocytes, without variation in the NG2+ precursor cells. Finally, a possible mechanism involving oligodendrocyte survival was demonstrated by the impaired intracellular transport of the PLP/DM20 myelin protein which was accompanied by cellular loss, suggesting stress-induced apoptosis. These findings describe a previously uncharacterized in vivo functional role for LPA1 in the regulation of oligodendrocyte differentiation and myelination in the CNS, underlining the importance of the maLPA1-null mouse as a model for the study of demyelinating diseases