Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the “culprits” were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount.Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties.Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance.There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear.Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.

Objective: Alterations in lipids in muscle and plasma have been documented in insulin‐resistant people with obesity. Whether these lipid alterations are a reflection of insulin resistance or obesity remains unclear.Methods: Nondiabetic sedentary individuals not treated with lipid‐lowering medications were studied (n = 51). Subjects with body mass index (BMI) > 25 kg/m² (n = 28) were stratified based on median glucose infusion rate during a hyperinsulinemic‐euglycemic clamp into insulin‐sensitive and insulin‐resistant groups (above and below median, obesity/insulin‐sensitive and obesity/insulin‐resistant, respectively). Lean individuals (n = 23) served as a reference group. Lipidomics was performed in muscle and plasma by liquid chromatography electrospray ionization‐tandem mass spectrometry. Pathway analysis of gene array in muscle was performed in a subset (n = 35).Results: In muscle, insulin resistance was characterized by higher levels of C18:0 sphingolipids, while in plasma, higher levels of diacylglycerol and cholesterol ester, and lower levels of lysophosphatidylcholine and lysoalkylphosphatidylcholine, indicated insulin resistance, irrespective of overweight/obesity. The sphingolipid metabolism gene pathway was upregulated in muscle in insulin resistance independent of obesity. An overweight/obesity lipidomic signature was only apparent in plasma, predominated by higher triacylglycerol and lower plasmalogen species.Conclusions: Muscle C18:0 sphingolipids may play a role in insulin resistance independent of excess adiposity.

Diabetes (type 2) and sensorineural hearing loss are common health problems manifested with ageing. While both type 1 and type 2 diabetes have been associated with hearing loss, a causal link has been difficult to establish. Individuals with diabetes have twice the incidence of hearing loss compared to those without diabetes and those with prediabetes have a 30% higher rate of hearing loss. Whether hearing loss is associated with diabetes independent of glycemic control remains to be determined. Hearing loss has its own set of risk factors and shares others with diabetes. This review will summarize the complex relationship between diabetes and sensorineural hearing loss.

Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance.

Objective. In this work we studied the correlation between platelet count, platelet activation, and systemic inflammation in overweight, obese, and morbidly obese individuals. Methods and subjects. A total of 6319 individuals participated in the study. Complete blood counts, high sensitivity C‐reactive protein (hs‐CRP) serum levels, and body mass index (BMI) were measured during routine checkups. Platelet activation markers were studied among 30 obese (BMI = 41 ± 8 kg/m²) and 35 nonobese (BMI = 24 ± 3 kg/m²) individuals. Platelet activation status was evaluated by flow cytometry using specific antibodies against the activated platelet membrane glycoprotein IIb/IIIa, p‐selectin (CD‐62 p), and binding of Annexin‐V to platelet anionic phospholipids. Results. Overweight, obese, and morbidly obese females had significantly elevated platelet counts (P < .0001) compared with normal‐weight females. No significant elevation of platelet counts was observed in the male subgroups. A significant age adjusted correlation between BMI and platelet counts (P < .0001) was found among females. This correlation was attenuated (P = .001) after adjustment for hs‐CRP concentrations. The flow cytometry analysis of platelets showed no significant differences in activation marker expression between nonobese and obese individuals. Discussion. Obesity may be associated with elevated platelet counts in females with chronic inflammation. Obesity is not associated with increased platelet activation.