UNASSIGNED: While effective, DAc injections for submental fat (SMF) reduction carry risks, including vascular damage and skin necrosis when improperly administered. This study presents a novel approach to SMF reduction using blunt microcannulas for DAc injections, coupled with 3D stereophotogrammetry quantification (3D-SQ).
UNASSIGNED: A 47-year-old female with SMF underwent two DAc applications. 3D-SQ was performed before and after each treatment using a 3D-SQ system. The patient experienced a substantial total volume reduction of 14.81 mL in the submental area after two DAc applications. 3D-SQ analysis showed a gradual reduction in submental volume over time. Importantly, no serious adverse events were reported, with only minor pain and warmth at the treated site. The reduction of SMF through DAc injections involves adipocyte cell lysis, emphasizing the importance of proper injection technique to avoid adverse events. The use of blunt microcannulas offers a safer alternative, minimizing the risk of skin necrosis, ulceration, and intra-arterial injections. Additionally, cannulas reduce bruising due to their blunt design and fan technique, enhancing patient comfort and safety.
UNASSIGNED: This case report highlights the efficacy of a novel cannula approach for DAc SMF reduction, assessed by 3D-SQ. Blunt microcannulas may represent a safer option compared to hypodermic needles, reducing the likelihood of severe complications.

Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population.
We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms.
We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05).
Genes related to lipolysis, redox reaction, and proliferation of islet β-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.

A benign soft tissue tumor of mature fat cells is called a lipoma (adipocytes). Lipoma can develop anywhere on the body, although it is uncommon in the mouth. Lipomas that are superficially positioned are often yellowish in color, painless, soft, and non-fluctuating with a thin epithelial surface. As a result, a delicate pattern of blood vessels is frequently seen on the surface. Deeper lesions might not exhibit this finding and, as a result, are not as clinically recognized. Since the patients do not report any subjective clinical symptoms, the dentist often diagnoses such lipomas by accident. Deep-seated lipomas require specialist imaging procedures, such as contrast-enhanced computed tomography, magnetic resonance imaging, or ultrasound to determine their extent. Lipomas can range in size from tiny to large to enormous. Large lipomas typically feature a \"slip sign\" and a nodular surface. Giant-sized lipomas can have a diameter of up to 10 cm. Lipomas can be single or multicellular. Dercum\'s disease, Proteus syndrome, neurofibromatosis, and familial adenomatosis polyposis all exhibit lipomas in various locations. The preferred course of treatment for these oral lipomas is surgical removal. Such lipomas do not recur again. Lipoma comes in a number of tiny varieties. The traditional description is of a well-defined tumor made up of lobules of uniformly sized and shaped mature fat cells. The term \"fibrolipoma\" refers to lipomas that contain a sizable amount of fibrous connective tissue, \"angiolipoma\" refers to lipomas that contain numerous tiny blood vessels, \"myxolipoma\" refers to lipomas with a background of myxoid cells, and \"spindle cell lipoma\" refers to lipomas that contain a mixture of uniform spindle cells. When compared to a pleomorphic liposarcoma, the pleomorphic lipoma exhibits spindle cells and strange, hyperchromatic large cells, making it challenging for the pathologist to tell them apart. An intramuscular lipoma is a lipoma that invades skeletal muscle bundles. Because they are harder to entirely eradicate, intramuscular lipomas are more likely to reoccur.

As the popularity of injection lipolysis increases, several side effects of injection lipolysis have been reported. In this case, A 53-year-old woman visited our outpatient clinic with a new round-shaped protruding mass (size: 5.0 cm × 3.0 cm) in the submental area. The patient had received the injection lipolysis treatment before the visit. She had received injections in the submental area at 1-week intervals (i.e., 4, 5, and 6 weeks). We performed contrast-enhanced computed tomography of the neck for differential diagnosis and found a 5.0 cm × 3.7 cm × 2.1 cm rim-enhanced fluid-density lesion in the submental. Hence, surgical removal of the lesion was planned based on the diagnosis of unspecified complicated fluid collection. The removed mass was a 3.0 cm × 2.0 cm × 2.0 cm whitish fibrous tissue. Histological examination revealed mucormycosis infection. Although several side effects of lipolysis have been reported to date, mucormycosis infection in the submental area has not been reported before.

BACKGROUND: It is commonly accepted that in obesity free fatty acids (FFA) cause insulin resistance and hyperglycemia, which drives hyperinsulinemia. However, hyperinsulinemia is observed in subjects with normoglycaemia and thus the paradigm above should be reevaluated.
METHODS: We describe two studies: MD-Lipolysis, a case control study investigating the mechanisms of obesity-driven insulin resistance by a systemic metabolic analysis, measurements of adipose tissue lipolysis by microdialysis, and adipose tissue genomics; and POEM, a cohort study used for validating differences in circulating metabolites in relation to adiposity and insulin resistance observed in the MD-Lipolysis study.
RESULTS: In insulin-resistant obese with normal glycaemia from the MD-Lipolysis study, hyperinsulinemia was associated with elevated FFA. Lipolysis, assessed by glycerol release per adipose tissue mass or adipocyte surface, was similar between obese and lean individuals. Adipose tissue from obese subjects showed reduced expression of genes mediating catecholamine-driven lipolysis, lipid storage, and increased expression of genes driving hyperplastic growth. In the POEM study, FFA levels were specifically elevated in obese-overweight subjects with normal fasting glucose and high fasting levels of insulin and C-peptide.
CONCLUSIONS: In obese subjects with normal glycaemia elevated circulating levels of FFA at fasting are the major metabolic derangement candidate driving fasting hyperinsulinemia. Elevated FFA in obese with normal glycaemia were better explained by increased fat mass rather than by adipose tissue insulin resistance. These results support the idea that hyperinsulinemia and insulin resistance may develop as part of a homeostatic adaptive response to increased adiposity and FFA.
BACKGROUND: Swedish-Research-Council (2016-02660); Diabetesfonden (DIA2017-250; DIA2018-384; DIA2020-564); Novo-Nordisk-Foundation (NNF17OC0027458; NNF19OC0057174); Cancerfonden (CAN2017/472; 200840PjF); Swedish-ALF-agreement (2018-74560).

OBJECTIVE: Lipid suspensions have been shown to be a suitable bio-enabling formulation approach for highly lipophilic or \'grease ball\' drug molecules, but studies on \'brick dust\' drugs are lacking. This study explored the utility of lipid suspensions for enhancing oral bioavailability of the rather hydrophobic drug nilotinib in vivo in rats.
METHODS: Four lipid suspensions were developed containing long chain triglycerides, medium chain triglyceride, long chain monoglycerides and medium chain monoglycerides and in vivo bioavailability was compared to an aqueous suspension. Additionally, in vitro lipolysis and wettability tests were conducted.
RESULTS: Nilotinib lipid suspensions did not show a bioavailability increase compared to an aqueous suspension. The bioavailability was lower for triglyceride suspensions, relative to both monoglyceride and an aqueous suspension. The long chain monoglyceride displayed a significantly higher bioavailability relative to triglycerides. In vitro lipolysis results suggested entrapment of nilotinib crystals within poorly dispersible triglycerides, leading to slower nilotinib release and absorption. This was further supported by higher wettability of nilotinib by lipids.
CONCLUSIONS: Monoglycerides improved oral bioavailability of nilotinib in rats, relative to triglycerides. For \'brick dust\' drugs formulated as lipid suspensions, poorly dispersible formulations may delay the release of drug crystals from the formulation leading to reduced absorption. Graphical Abstract An aqueous and four lipid suspensions have been evaluated in in vitro and in vivo to gain insights into the potential benefits and limitations of lipid suspensions.

Enzymatic digestion of lipid drug carriers is very important. Commonly, pancreatin induced formation of fatty acids is monitored by the pH-stat method, which provides a fast, but unspecific readout. However, according to the literature, the pKa values of long chain fatty acids are strongly dependent on the local environment and might vary between 4.2 and 10.15. The high pKa values would lead to an incomplete detection of the lipid digestion and false results. In order to investigate these issues in more detail, we produced cetyl palmitate solid lipid nanoparticles (CP-SLN) stabilized with poloxamer 188 or polysorbate 80. The digestion of CP-SLN was investigated by two different and independent readouts. A HPTLC assay was used in addition to the pH-stat method (with or without back titration). An incomplete digestion of CP-SLN was observed with all methods. Partial digestion of polysorbate 80 contributed to the formation of fatty acids. Depending on the investigated system and the experimental conditions (FaSSIF or FeSSIF) the results of both readout methods were comparable or not. For example, in FeSSIF conditions, the values detected by HPTLC were roughly twice as high as the pH-stat results. Our findings on solid lipids agree with data from Helbig et al. on lipid emulsions, where a gas chromatography method detected much higher values than the pH-stat assay (Food Hydrocoll. 28 (2012) 10-19). The results of our pH-stat experiments with back titration at different pH values showed increased values for fatty acids from pH 7.5 to pH 10. The values obtained by back titration at high pH values (pH 9 or higher) did exceed the digestion values measured by HPTLC. Therefore, we conclude that the pH-stat method might give the same results as more specific reference methods, but it might also both under- (without back titration) or overestimate (with back titration) the enzymatic digestion of lipid drug delivery systems. A further outcome of our study was the proof that lipase is the main enzyme involved in the digestion of the solid wax cetyl palmitate, because CP-SLN loaded with the inhibitor orlistat were not digestible and gave similar values as the corresponding control samples. In summary, our experimental results confirm the theoretical considerations (based on published pKa values) that the pH-stat method will not detect all fatty acids quantitatively. The very strong impact of the local environment on the pKa value of long chain fatty acids is a serious limitation and might lead to misleading interpretations.

The aim of this study was to investigate if molecular interactions between the weak base cinnarizine and lipolysis products were affecting the morphology of precipitated drug formed during in vitro lipolysis. In vitro lipolysis studies of a self-nanoemulsifying drug delivery system with or without cinnarizine were conducted. The digestion phases (aqueous phase and pellet phase) were separated by ultracentrifugation, and the pellet was isolated and lyophilized. The lyophilized pellets were examined by X-ray powder diffraction, (13)C solid-state nuclear magnetic resonance ((13)C NMR), (1)H liquid-state NMR ((1)H NMR) spectroscopy and differential scanning calorimetry (DSC). The (13)C NMR data indicated that the carbonyl groups and aliphatic part of the lipids undergo structural changes when the pellet contains cinnarizine. The (1)H NMR data suggests interactions occurring around the nitrogens on cinnarizine and the carboxylic group of fatty acids. DSC thermograms showed cinnarizine to be homogeneously incorporated into the lipids of the pellet, and no free amorphous cinnarizine was present. The three techniques (13)C NMR, (1)H NMR, and DSC complement each other and suggest interactions to occur between fatty acids and cinnarizine, which in turn favors amorphous precipitation.

Silica-lipid-mannitol hybrid (SLMH) microparticles have been developed that were compressible into high quality tablets suitable for oral dosing and delivery of poorly soluble drugs. SLMH tablets enable high lipid-loading levels (>40%) and retain the immediate release, enhanced lipase digestion and drug solubilisation performance. Specifically, we report formulation optimisation of SLMH microparticles and tablets using coumarin 102 (log P = 4.09) as a model Biopharmaceutics Classification System class II drug. SLMH tablets were acceptable according to standard British Pharmacopoeia friability, hardness and disintegration tests; this is not the case for conventional dry emulsions. Furthermore, in vitro dissolution and pancreatic-lipase-induced lipolysis studies under simulated intestinal conditions have demonstrated enzymatic-digestion-mediated drug solubilisation. SLMH microparticles and tablets are suitable as liquid lipid containing solid dosage forms for enhancing and controlling oral absorption of poorly soluble drugs.

Elevation in non-esterified fatty acids (NEFA) has been shown to modulate insulin secretion and it is considered as a risk factor for the development of type 2 diabetes. Here we present a method that complements a mathematical model of NEFA kinetics with genetic algorithms for model identification. The complemented strategy allowed to assess parameters of NEFA kinetics and to get insight into their relationship with insulin during oral glucose tolerance tests in women with former gestational diabetes: (i) providing a reliable estimation of the model parameters, (ii) assuring the usability of the model, and (iii) promoting and facilitating its application in a clinical context.