Effect of intensive insulin therapy on progression of overt nephropathy in patients with type 1 diabetes mellitus.

OBJECTIVE: To assess the effects of chronic (long-term) intermittent intravenous insulin therapy (CIIIT) on the progression of overt nephropathy in patients with type 1 diabetes mellitus. METHODS: We undertook a retrospective longitudinal three-center study of 31 patients with type 1 diabetes mellitus and overt nephropathy, who were receiving intensive subcutaneous insulin therapy (four insulin injections daily) and weekly CIIIT. All study patients had follow-up consultations weekly for at least 12 months (mean duration, 37.0 +/- 4.6 months). Each patient had monthly hemoglobin A(1c) (by high-performance liquid chromatography) and semiannual creatinine clearance determinations. RESULTS: The hemoglobin A(1c) levels declined significantly from 8.6 +/- 0.6% to 7.6 +/- 0.3% (P = 0.0062) during the study period. The creatinine clearance remained essentially unchanged (from 46.1 +/- 3.0 mL/min per 1.73 m 2 at baseline to 46.0 +/- 3.9 mL/min per 1.73 m 2 at the end of the observation period, with an average annualized slope increase of 3.39 +/- 1.5 mL/min per year--no significant difference). CONCLUSION: The addition of CIIIT to intensive subcutaneous insulin therapy in patients with type 1 diabetes mellitus seems to arrest or appreciably reduce the progression of overt diabetic nephropathy, as well as substantially improve their glycemic control.

Effect of intensive insulin therapy on abnormal circadian blood pressure pattern in patients with type I diabetes mellitus.

OBJECTIVE: To assess the effect of tight glycemic control on the abnormal circadian BP pattern associated with IDDM. DESIGN: Retrospective, randomized control trial. SETTING: Diabetes Research Institute, ambulatory. PATIENTS: Seventy-four IDDM patients (22M/52F) on intensive subcutaneous insulin therapy (ISIT) were selected for this study. INTERVENTIONS: Group A patients (11M/25F) underwent, in addition to ISIT, weekly chronic intermittent intravenous insulin therapy (CIIIT) (TT Aoki et al, Lancet, 1993, 432:515-8). Group B patients (11M/27F) were continued on ISIT alone. All study patients were followed for 3 months on this regimen. They were seen weekly by the investigators and underwent monthly HbA1c determinations and 24-h ambulatory BP monitoring. RESULTS: Glycemic control improved significantly in group A subjects (HbA1c decreased from 7.9% to 7.2%, p = 0.0002) but changed little in the group B subjects (p = NS). The night/day systolic BP ratio decreased from 0.97 to 0.94 (-3.10%) in group A and increased from 0.95 to 0.98 (+3.16%) in group B subjects (p = 0.224). The night/day diastolic ratio decreased from 0.93 to 0.90 (-3.23%) in group A and increased from 0.91 to 0.94 (+3.29%) in group B subjects (p = 0.0037). CONCLUSIONS: CIIIT performed in IDDM patients on ISIT further improves their glycemic control and tends to reverse or at least prevent further deterioration of their abnormal circadian BP pattern.

Effect of chronic intermittent intravenous insulin therapy on antihypertensive medication requirements in IDDM subjects with hypertension and nephropathy.

OBJECTIVE: The prevalence of systemic hypertension is increased in patients with diabetes. In this prospective, randomized, crossover clinical trial, we assessed antihypertensive effects of chronic intermittent intravenous insulin therapy (CIIIT) on insulin-dependent diabetes mellitus (IDDM) subjects with hypertension and nephropathy by monitoring the amount of antihypertensive medication (AHM) required to maintain blood pressure (BP) < or = 140/90 mmHg. RESEARCH DESIGN AND METHODS: After a stabilization period, 26 hypertensive IDDM subjects were randomly assigned to a control or treatment phase for 3 months and then crossed over into the opposite phase for another 3 months. Addition of CIIIT during the treatment phase was the only procedural difference between the control and treatment phases. RESULTS: The AHM dosage requirements for maintenance of the baseline BP levels decreased significantly (46%; P < 0.0001) and linearly over time (P < 0.0058) during the treatment phase, while remaining essentially unchanged during the control phase. CONCLUSIONS: Our data suggest that CIIIT markedly improves BP control, as evidenced by the significantly reduced AHM dosage requirements in subjects with IDDM and hypertension, possibly through an improvement in vascular reactivity.