The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus

Abstract

Summary. Glomerular filtration rate, renal plasma flow, urinary excretion of fl-2-microglobulin and albumin, heart rate and blood pressure were studied in eight young male insulin-dependent diabetics. Measurements were performed before and during insulin infusion at 2 mU/kg/min: No patient had discernible insulin antibodies. Two studies were performed at random in each patient. In series A blood glucose concentration was allowed to decline, while in series B it was maintained at a constant level. Ten 20 min clearance periods were performed, four before and six during insulin infusion. Results are given as mean+SEM of .values from the first four (control) and last four (test) clearance periods. Blood glucose declined in series A experiments from 10.8_+0.8 mmol/1 in the control period to 5.8+0.5 mmol/1 during the test period, but remained constant during experiment B (9.8+ 1.1 and 9.5_+ 1.1 mmol/1). Plasma insulin levels were comparable in the two series. GIomerular filtration rate fell from 141+7 ml/ min • 1.73 m 2 to 132_+7 ml/min X 1.73 m 2 (p < 0.01) in series A but did not change significantly during series B. Similarily renal plasma flow declined with declining glucose but remained constant when glucose was maintained at a constant level. In series A the magnitude of decrease in renal plasma flow was correlated with the magnitude of decrease in glomerular filtration rate (r = 0.95, p < 0.001). fl-2-microglobulin excretion decreased significantly (p < 0.05) in both series (A: 89+17 to 60_+13 ng/min, B: 117_+46 to 62_+17ng/min). Albumin excretion increased in five out of six patients with normal control values (not significant) in series A and in four out of six in series B. No significant changes in heart rate or blood pressure were observed. Thus insulin infusion reduced renal plasma flow and glomerular filtration rate, but this effect could be completely abolished by keeping blood glucose constant. This suggests that it is not the lack of insulin but the associated hyperglycaemia which contributes to the elevated renal plasma flow and glomerular filtration rate in insulin-dependent diabetics.

Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics

“…Recently we found GFR and RPF elevated to nearly the same extent in another group of IDD patients comparable to the present group of patients -also with respect to metabolic control [13], (Table 3). Elevated GFR is a well established feature in short-term IDD [4,14].…”

“…They were admitted to hospital 10-14 days prior to the clearance studies for further improvement of their metabolic control. No such attempts were made in the present or in our previous study [13]. Table 3 shows that mean bloodglucose and 24-hour urinary glucose excretion were significantly lower in the IDD patients with normal RPF compared with the two other groups.…”

“…Ditzel and Junker found a reduced RPF [14]. The RPF was measured in the morning after the patients had received their usual insulin dose at 0700 h. Recent studies have demonstrated that insulin reduces RPF in short-term IDD [13,15]. Mogensen [4] demonstrated a significantly elevated RPF (+ 10%) in 28 short-term diabetic Patients compared with 31 age and sex matched normal subjects.…”

Acute effects of insulin on cardiovascular function and noradrenaline uptake and release

“…Intravenous in: jection of insulin (in a dose which did not result in hypoglycaemia) decreased glomerular filtration rate and renal blood flow in diabetic patients [8] but, if the fall in blood glucose was prevented by infusion of glucose, renal blood flow and glomerular filtration rate did not change [8]. Previously, Brochner-Mortensen showed that intravenous infusion of glucose in normal subjects increased glomerular filtration rate [9], findings which have been confirmed by others [10,11]. Thus, hyperglycaemia per se is at least partially responsible for the elevated glomerular filtration rate observed in many diabetic patients.…”

The relationship between kidney size and function in short-term diabetic patients

“…It is documented that GFR in Type 1 diabetic patients can be increased or decreased within minutes in response to physiological changes in plasma levels of insulin, glucose and glucagon [6][7][8][9][10]. It is extremely unlikely that changes in kidney size can account for these rapid changes in GFR.…”