A pilot study on the effect of telmisartan & ramipril on 24 h blood pressure profile & dipping pattern in type 1 diabetes patients with nephropathy.

Background & objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern. Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria. Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study. Interpretation & conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

Validation of bedside methods in evaluation of diabetic peripheral neuropathy.

Background & objectives: Vibration perception threshold (VPT) is considered as a gold standard for diagnosis of diabetic peripheral neuropathy. However, the data are sparse comparing the VPT with commonly used bedside modalities. This study was carried out to evaluate the usefulness of simple bed side screening modalities for peripheral neuropathy in patients with diabetes mellitus. Methods: A total of 1044 patients with diabetes mellitus attending the Diabetes clinic from January 2007 to May 2008, were included in this study. All subjects had a detailed clinical assessment including Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathy Examination (DNE) score, ankle reflex, vibration sensation with a 128 Hz tuning fork, 10g Semmes-Weinstein monofilament and vibration perception threshold (VPT). Results: The prevalence of peripheral neuropathy was 34.9 per cent with VPT. Foot care practices were followed by only 214 (20.5%) of the study population. When compared with VPT, ankle reflex was the most sensitive (90.7%) but least specific (37.3%). The tuning fork and monofilament tests respectively had lower sensitivity (62.5 and 62.8%) but better specificity (95.3 and 92.9%) and accuracy (78.9 and 77.9%). Significant correlations were observed between the VPT score and the DNE (r = 0.532, P<0.001) and DNS (r = 0.546, P<0.001) scores and absent tuning fork sensation (r= 0.590; P<0.001), monofilament sensation (r= 0.573; P<0.001) and ankle reflex (r = 0.377, P= 0.01). Interpretation & conclusions: The present findings show that simple bed side tests are useful for assessing peripheral diabetic neuropathy, even in those subjects in whom foot care practices are not followed.

Anti-albuminuric efficacy of a combination of angiotensin converting enzyme inhibitor & angiotensin receptor blocker in type 1 DM with nephropathy.

Background & objective: The efficacy of the combination of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors in patients of type 1 diabetes mellitus (DM) with nephropathy is debatable. The antialbuminuric efficacy of dual blockade in patients of type 1 DM with micro- or macroabuminuria were evaluated. Methods: In this open label observational study 30 patients (20 male 10 female) with type 1 DM were included who were initially treated with telmisartan 80 mg for eight weeks followed by addition of ramipril 10 mg for a further eight weeks. Albuminuria reduction was studied at the end of each phase. Results: Therapy with telmisartan for 8 wk resulted in a 39 per cent (P<0.01) reduction in albumin excretion rate (AER). Combination therapy with telmisartan and ramipril produced a further reduction in AER of 33.4 per cent (P<0.01), amounting to a total AER reduction of 59 per cent (P<0.001). Dual blockade was more effective in the group of macroalbuminuric as compared to microalbuminuric subjects (P<0.05). Telmisartan produced a significant reduction in SBP (P<0.05). The addition of ramipril produced a further reduction in BP, the total reduction being 10.3 in SBP and 7.2 mmHg in DBP (P<0.001 for both). There was an increase in mean serum potassium of 0.39 mmol/l (P<0.01) from baseline at the end of the study period and two patients had hyperkalemia > 5.5 mmol/l with dual blockade. Interpretation & conclusion: Dual blockade with ramipril enhanced the antialbuminuric efficacy of telmisartan and further reduced blood pressure. The effect of dual blockade was more pronounced in the macroalbuminuric subjects and it was well tolerated. However, careful monitoring of serum potassium is required.