With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight‐management clinic and 11 lean healthy controls. Patients were classified into metabolically “healthy obese” (n = 26; mean age 42.6 years, mean BMI 46.8 kg/m2) or “unhealthy obese” (n = 26; mean age 45 years, mean BMI 47.5 kg/m2) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.

Background/Aims: Urinary biomarkers can identify damage to specific parts of the nephron. We performed a cross-sectional study to characterise the pattern of diabetic nephropathy using urinary biomarkers of glomerular fibrosis (collagen IV), proximal tubular damage (α-glutathione-S-transferase, GST) and distal tubular damage (πGST). Methods: Clinical data from 457 unselected patients attending a hospital diabetes clinic were collected. Spot urine samples were analysed for albumin and creatinine. Biomarkers were measured by enzyme-linked immunosorbent assay, and corrected to urinary creatinine. Results: All 3 biomarkers correlated weakly with albumin/creatinine ratios (Pearson correlation <0.2, p values <0.001). The most common abnormality was elevated urinary collagen IV (glomerular, 35%) compared to αGST (proximal tubule, 18%) or πGST (distal tubule, 15%). The proportion of patients with abnormal biomarker results increased across the normo-, micro- and macroalbuminuria groups, with collagen IV (26, 58, 65%) and πGST (11, 25, 35%) but not αGST. Conclusion: In patients with diabetes, these urinary biomarkers appear to identify renal damage that is related to, but distinct from, urine albumin/creatinine ratios. The markers of glomerular fibrosis and distal tubular damage related most closely to the degree of albuminuria. Longitudinal studies are now required to assess whether these biomarkers can detect early renal disease with greater specificity and sensitivity than the albumin/creatinine ratio.

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