Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment.

Our longitudinal study of urinary albumin excretion rate in long-term insulin-dependent diabetics without proteinuria (negative albustix) suggests that early detection of patients at high and low risk of developing persistent proteinuria, i.e., diabetic nephropathy, is possible by using a sensitive method for albumin determination. Our prospective studies in young insulin-dependent diabetics with diabetic nephropathy show that the rate of decline in glomerular filtration rate (GFR) varies considerably, with a mean of 0.75 ml/min/mo and a range from 0.1 to 1.50 ml/min/mo, and that an increase in arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy.

[Clinical consequences of intranasal insulin therapy in insulin-dependent diabetes mellitus]. / Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus.

Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control, assessed by haemoglobin A1c concentrations, deteriorated after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.

Clinical experience with NovoPen II and insulin Protaphane HM Penfill.

The acceptance and convenience of an intermediate acting insulin Protaphane HM in Penfill were evaluated and compared with vials, and the safety of administration in Penfill was tested in 19 insulin-dependent diabetes mellitus patients. The design was a randomized, cross-over within-patient comparison with a run-in period of 4 weeks and two 12-week study periods. Safety was assessed by 7 point blood glucose profiles, HbA1c, total insulin dosage and frequency of hypoglycaemic episodes. Acceptance and convenience were evaluated by a questionnaire. None of the differences was statistically significant. Seventeen out of the 19 patients found NovoPen easier and quicker to use than conventional syringes and needles. The acceptance of a new pen device, NovoPen II, was tested in 56 insulin-dependent diabetes mellitus patients. Fifty-two out of 55 patients who completed a questionnaire preferred to continue with NovoPen II and 51 found it easy to preselect the dose. In conclusion, insulin Protaphane HM in Penfill can be safely administered with the NovoPen system.

Auscultatory measurement of blood pressure performed by the doctor on duty.

A review is presented of the measurements of blood pressure on admission of 600 patients to the wards in a department of general medicine. Three doctors each examined 200 patients, distributed over two periods with an interval of one year. Large differences were found between the doctors as regards the distribution of the BPs, particularly the diastolic pressures. On the other hand, no differences were observed in the distributions during the two periods as far as the individual doctors were concerned. Great preference was shown for zero as the terminal digit and also for certain BP values. It is concluded that the observer introduces a considerable subjective factor in measuring the BP by auscultation. Correct performance of this simple procedure requires meticulous instruction.

Incipient nephropathy in type 1 (insulin-dependent) diabetes.

Patients with Type 1 (insulin-dependent) diabetes without proteinuria were studied to define those patients who will later develop persistent proteinuria (more than 0.5 g protein/24 h). Two investigations were performed; 71 patients were studied longitudinally for 6 years and another 227 patients were studied cross-sectionally. All were less than 50 years of age and had developed diabetes before the age of 40 years. At entry into the study they had no proteinuria (Albustix method), had normal blood pressure and urinary albumin excretion rates less than 200 micrograms/min (normal less than or equal to 20 micrograms/min). The best predictor of persistent proteinuria or an albumin excretion rate greater than 200 micrograms/min was the initial urinary albumin excretion rate. During the longitudinal study, seven patients with an urinary albumin excretion rate of more than 70 micrograms/min at the start of the study developed persistent proteinuria or an albumin excretion rate greater than 200 micrograms/min. In contrast, only three out of the remaining 64 patients with urinary albumin excretion rate less than or equal to 70 micrograms/min developed urinary albumin excretion rate greater than 200 micrograms/min. Patients with an urinary albumin excretion rate greater than 70 micrograms/min are thus at risk of developing diabetic nephropathy. We designate this stage of renal involvement incipient nephropathy. Patients with incipient nephropathy were further characterized in the cross-sectional study. Compared with normoalbuminuric patients, patients with incipient nephropathy had increased systolic and diastolic blood pressure, but normal serum creatinine. The glomerular filtration rate was higher than normal in patients with incipient nephropathy though not different from that of normoalbuminuric patients.

Diabetic nephropathy and arterial hypertension.

The relationship between arterial blood pressure and diabetic nephropathy was examined in 61 Type 1 (insulin-dependent) diabetic patients (22 females and 39 males). All patients fulfilled the following criteria: persistent proteinuria (greater than 0.5 g/day), onset of diabetes before 31 years of age, age less than 42 years, serum creatinine less than 130 mumol/l, and no antihypertensive treatment. Thirty Type 1 diabetic patients without persistent proteinuria but matched for sex, age, ideal body weight and duration of diabetes, and 30 healthy subjects matched for sex, age and ideal body weight were also studied as controls. The diabetic patients with persistent proteinuria had elevated blood pressures (146/96 +/- 17/10 mmHg, mean +/- SD) compared with 123/75 +/- 11/8 mmHg in diabetic patients without persistent proteinuria, and normal subjects (120/77 +/- 6/6 mmHg; p less than 0.001 for each). Diastolic blood pressure greater than or equal to 95 mmHg was found in 51% of the group with persistent proteinuria. Elevated arterial blood pressure is frequently present in young Type 1 diabetic patients with diabetic nephropathy and normal serum creatinine.

Intranasal insulin therapy: the clinical realities.

To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.