Is there an impact of treatment with DPP-4 inhibitors on lymphocyte subpopulations in type 2 diabetic patients?

INTRODUCTION: Dipeptidil peptidase 4 inhibitors (DPP-4) are a group of antihyperglycemic agents. DPP-4 is an enzyme expressed on lymphocyte surface as co-stimulatory molecule in activation processes. The aim was to assess lymphocyte subpopulations initially and after 14 days of treatment with DPP-4 inhibitors sitagliptin, saxagliptin and vildagliptin. MATERIAL AND METHODS: The study was conducted in three groups 10 subjects each, of type 2 diabetic patients. In subjects studied an initial tests followed by repeated ones after 14 days of treatment with sitagliptin, saxagliptin, and vildagliptin in therapeutic doses were performed. Baseline test as well as lymphocyte subpopulations (total T cells, and T-cell subsets CD4+, CD8+, CD26+, CD45RA+, CD45RO+, CD4+/CD25+) using 7-colour flow cytometry method were performed. RESULTS: In patients receiving sitagliptin no significant increase in lymphocyte subpopulations were observed. In patients who received vildagliptin significant increase of total T-cells (p < 0.05); in patients treated with saxagliptin significant (p < 0.05) though mild increased percentage of total T-cells and CD4+, CD26+, CD45RO+ subsets were found. CONCLUSIONS: The study showed mild but significant increase of several T-cell subsets after treatment with saxagliptin and vildagliptin with non significant elevation after treatment with sitagliptin. It seems that changes are not expressed enough to have a clinical impact.

Salt-sensitive blood pressure--an intermediate phenotype predisposing to diabetic nephropathy?

BACKGROUND: Family studies point to important genetic determinants of diabetic nephropathy (DN). Blood pressure (BP) is higher in offspring of patients with type 2 diabetes and DN, but the pathomechanisms involved have not been elucidated. METHODS: We examined the salt sensitivity of BP after 5 days equilibration on a low (20 mmol/day) vs high salt diet (220 mmol/day) in three matched groups of 15 subjects each: (i) control individuals; (ii) offspring of type 2 diabetic parents without DN (DN-); and (iii) offspring of type 2 diabetic parents with DN (DN+). Ambulatory BP and hormones involved in sodium homeostasis [plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP)] as well as the tetrahydrocortisol + 5-allotetrahydrocortisol/tetrahydrocortisone (THF + 5alphaTHF)/THE) ratio in the urine as an index of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) activity were analysed. RESULTS: In offspring of DN+ patients on a high salt diet, systolic and diastolic BP was 137/82+/-10/8 mmHg vs 125/77+/-12/8 mmHg in offspring of DN- patients (P<0.01 for systolic BP). The salt-induced difference in mean BP between high and low salt diet was 5.2+/-3.3 mmHg in offspring of DN+ patients vs 0.7+/-4.7 mmHg in offspring of DN- patients (P<0.002). The proportion of 'salt-sensitive' individuals was 67% in offspring of DN+ patients vs 20% in offspring of DN- patients (P<0.05). In all groups, a high salt diet caused a comparable decrease of PRA and p-aldosterone accompanied by an increase in ANP. The urinary (THF + 5alphaTHF)/THE ratio was 1.23+/-0.36 in salt-sensitive individuals and 0.99+/-0.33 (P<0.03) in salt-resistant subjects, consistent with increased activity of 11betaHSD2. CONCLUSIONS: BP is more salt sensitive in offspring of type 2 diabetic patients with diabetic nephropathy. The salt sensitivity of BP may be an intermediate phenotype in individuals with a high risk of future diabetic nephropathy.

Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy?

There is convincing evidence for a specific BP-independent effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular disease is not consistently halted by these agents, there is a need to explore potential renoprotective effects of other drugs. Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner. A randomized, crossover design was used to assess the human relevance of the experimental data in 15 normotensive, nonsmoking type 1 diabetic mellitus patients with good glycemic control (age, 37.3 +/- 6.6 yr; 9 men/6 women; duration of diabetes, 23.6 +/- 5.1 yr) with baseline urinary albumin excretion rates (AER) >20 microg/min in the run-in phase. AER was assessed in overnight timed urine collections. The patients were assigned to a 3-wk placebo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in random order. This dose causes modest BP lowering in hypertensive individuals but does not affect BP in normotensive individuals. There was no significant effect on ambulatory BP (mean arterial pressure, 91.8 +/- 7.1 mmHg in the third week of placebo and 91.1 +/- 8.7 mm Hg on moxonidine). There was a significant (P< 0.006) difference of the treatment effects between placebo and moxonidine, respectively, on AER; median AER at the end of the placebo period was 39.8 microg/min (range, 15.9 to 117 microg/min) versus 29.0 (range, 9.03 to 85.8 microg/min) at the end of the moxonidine period. The data document an antialbuminuric effect of nonhypotensive doses of moxonidine. Diminished sympathetic traffic to the kidney is the most plausible explanation for the finding.