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Summary. Glomerular filtration rate (GFR), renal plasma flow (RPF) and kidney volume were measured in thirteen male subjects (mean age 30 years) with short-term insulin-dependent diabetes (mean duration of disease 2.4 years) and fourteen normal male subjects (mean age 29 years). GFR and RPF were measured by constant infusion technique using I125-iothalamate and 13q-hippuran. Kidney size was determined by means of ultrasound. GFR, RPF and kidney volume were increased in the diabetic patients compared to the normal controls, 144 versus 113 ml/ min • 1.73 m 2 (p < 0.0005), 627 versus 523 ml/ min x 1.73 m 2 (p < 0.0025) and 278 versus 224 ml/ 1.73 m 2 (p < 0.0005) respectively. Combining results from diabetic patients and controls revealed a positive correlation between kidney size and GFR (r = 0.70, p < 0.001) and between kidney size and RPF (r = 0.61, p < 0.001). Within the groups kidney size and RPF correlated significantly in the diabetics (p < 0.01) and the same was found for kidney size and GFR (0.025< p < 0.05), while no correlations were found in the normal group. GFR and RPF correlated in the diabetics when evaluated separately (r = 0.81, p < 0.001) and in the controls (r = 0.73, p < 0.001). The previous and present data suggest that the mechanisms of the elevated GFR in insulin-dependent diabetics are enhanced RPF, increased transglomerular hydrostatic pressure gradient and increased glomerular ultrafiltration coefficient. The increased kidney size is probably the main cause of the above alterations in the GFR determinants.

BackgroundDespite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.Methodology/Principal FindingsOne hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA1c (HbA1c) ≥8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA1c after one year of treatment. At enrolment, mean (standard deviation) HbA1c was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA1c, 0.13% (−0.19; 0.44), p = 0.422; Total daily insulin dose, −5.7 U/day (−8.6; −2.9), p<0.001; body weight, −1.74 kg (−3.32; −0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.Conclusions/SignificanceIn patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.Trial RegistrationClinicalTrials.gov NCT00118937

The effect of intravenous glucose infusion on glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) and on urinary excretion of albumin and beta-2-microglobulin were studied in ten normal subjects and seven metabolically well-controlled insulin-dependent diabetics. Following glucose infusion in normal subjects (n = 10) blood glucose increased from 4.7 +/- 0.1 to 10.9 +/- 0.4 mmol/l (SEM) (p less than or equal to 0.01). Glomerular filtration rate increased from 116 +/- 2 to 123 +/- 3 ml/mi x 1.73 m2 (p less than or equal to 0.01), while no change in renal plasma flow was seen - 552 +/- 11 versus 553 +/- 18 ml/min x 1.73 m2. Volume expansion with intravenous saline infusion in six of the normal subjects induced no changes in blood glucose or kidney function. In seven strictly controlled insulin-dependent diabetics, blood glucose values were raised from 4.6 +/- 0.4 to 16.0 +/- 0.6 mmol/l and clamped by means of an 'artificial beta cell'. Glomerular filtration rate increased in all patients, from 133 +/- 5 to 140 +/- 6 ml/min x 1.73 m2 (p less than or equal to 0.02), as did renal plasma flow from 576 +/- 26 to 623 +/- 38 ml/min x 1.73 m2 (p less than or equal to 0.02). Urinary albumin excretion remained unchanged in both normal subjects and diabetics. beta-2-microglobulin excretion rate increased significantly in the diabetics following glucose infusion, while no significant change was seen in the normal subjects. Our results show that hyperglycaemia per se contributes to the increased glomerular filtration rate and renal plasma flow in insulin-dependent diabetes.