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Cancer survivors are at increased risk of type 2 diabetes, which usually develops from obesity and insulin resistance. Whether diabetes susceptibility is due to shared risk factors for cancer and insulin resistance or directly related to cancer and its treatment is unknown. We investigated effect modification between malignancy and body mass index (BMI) as determinants of insulin sensitivity in patients with hematologic malignancies and controls without cancer. In a cross-sectional study of 43 individuals without diabetes (20 patients with treated hematologic malignancies; 23 controls without malignancies), we measured insulin-stimulated whole-body glucose use (M) by hyperinsulinemic euglycemic clamp. Insulin sensitivity index (ISI) was calculated by dividing M over steady-state plasma insulin. Inflammatory cytokines were measured in plasma. Controls were more obese and included more non-White individuals and women vs patients with hematologic malignancies. Patients with cancer exhibited greater insulin sensitivity (median ISI, 42.4 mg/kg/min/[μU/mL]; interquartile range [IQR], 33.9-67.2 vs 23.4 mg/kg/min/[μU/mL]; IQR, 12.9-29.2; P < .001) and higher interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) concentrations vs controls. Patients with cancer demonstrated greater reduction in ISI with increasing BMI vs controls, which remained significant after adjustment for sex and race (β = −2.6 units; 95% confidence interval, −4.8 to −0.4; P interaction = .024). This interaction also remained significant after adjusting for log IL-6 (P interaction = .048) and log MCP-1 (P interaction = .021). Cancer survivors had disproportionately greater insulin resistance with increasing BMI vs controls without malignancies. Effect modification between cancer and BMI in determining insulin sensitivity implicated cancer-specific etiologies in glucose dysregulation and could partially explain excess diabetes diagnoses among oncology patients.

Obesity-associated inflammation is a systemic process that affects all metabolic organs. Prominent among these is adipose tissue, where cells of the innate and adaptive immune system are markedly changed in obesity, implicating these cells in a range of processes linking immune memory to metabolic regulation. Furthermore, weight loss and weight cycling have unexpected effects on adipose tissue immune populations. Here, we review the current literature on the roles of various immune cells in lean and obese adipose tissue. Within this context, we discuss pharmacological and nonpharmacological approaches to obesity treatment and their impact on systemic inflammation.

Cancer survivors are at increased risk for type 2 diabetes mellitus which usually develops from obesity and insulin resistance. It is unknown whether diabetes susceptibility is due to shared risk factors for cancer and insulin resistance or directly related to cancer and its treatment. We investigated the effect modification between malignancy and body mass index (BMI) as determinants of insulin sensitivity in patients with hematological malignancies and controls without cancer. In a cross-sectional study of 43 non-diabetic subjects (20 patients with treated hematological malignancies and 23 controls without malignancy) we measured insulin-stimulated whole-body glucose utilization (M) using hyperinsulinemic euglycemic clamps. Insulin sensitivity index (ISI) was calculated by dividing M over the steady-state plasma insulin. Inflammatory cytokines were measured in the plasma. Controls were more obese and included more non-whites and females compared to patients with hematological malignancies. Patients with cancer exhibited greater insulin sensitivity (median ISI, 42.4mg/kg/min/(µU/ml) [IQR, 33.9-67.2] vs. 23.4mg/kg/min/(µU/ml) [IQR, 12.9-29.2], P<0.001) and higher IL-6 and MCP-1 concentrations compared to controls. Patients with cancer demonstrated greater reduction in ISI with increasing BMI compared to controls, which remained significant after adjustment for genderand race (β=-2.6 units [95% CI: -4.8 to -0.4], P-interaction=0.024). This interaction also remained significant after adjusting for log IL-6 (P-interaction=0.048) and log MCP-1 (P-interaction=0.021). Cancer survivors have disproportionately greater insulin resistance with increasing BMI compared to controls without malignancy. The effect modification between cancer and BMI in determining insulin sensitivity implicates cancer-specific etiologies in glucose dysregulation and could partially explain excess diabetes diagnoses among oncology patients.

Persons with HIV are at increased risk for diabetes mellitus compared with individuals without HIV. Adipose tissue is an important regulator of glucose and lipid metabolism, and adipose tissue T cells modulate local inflammatory responses and, by extension, adipocyte function. Persons with HIV and diabetes have a high proportion of CX3CR1+GPR56+CD57+(C-G-C+) CD4+T cells in adipose tissue, a subset of which are cytomegalovirus specific, whereas individuals with diabetes but without HIV have predominantly CD69+CD4+T cells. Adipose tissue CD69+and C-G-C+CD4+T cell subsets demonstrate higher receptor clonality compared with the same cells in blood, potentially reflecting antigen-driven expansion, but C-G-C+CD4+T cells have a more inflammatory and cytotoxic RNA transcriptome. Future studies will explore whether viral antigens have a role in recruitment and proliferation of pro-inflammatory C-G-C+CD4+T cells in adipose tissue of persons with HIV.