Glomerular hyperfiltration in insulin-dependent diabetes mellitus is correlated with enhanced growth hormone secretion.

Abstract

Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability.

Changes in the Growth Hormone‐IGF‐I Axis in Non‐obese Diabetic Mice

“…This is contrary to what has been described in humans (Blankestijn et al, 1993;Press et al, 1984;Hayford et al, 1980). In addition, typical diabetic glomerulosclerosis associated with increasing azotemia does not develop, even in longterm follow-up models.…”

Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of IGF type 1 receptor activation

“…4). JAK2 phosphorylation, which is required for GH induced activation of STAT3, was not increased in DM, suggesting that the increase in pSTAT3 is caused by another member of the cytokine family signaling through a JAK other than JAK2 or possibly through the mTOR pathway [20,26], which we found to be hyperactive (Fig. 7c).…”

“…Human type 1 DM is characterized by an increase in circulating GH and an inverse correlation between glycemic control and serum GH levels [20,21]. Several rodent studies have shown that inhibition of GH has preventive effects on the development of diabetic nephropathy.…”

The place of pegvisomant in the management of acromegaly

“…Studies addressing the effect of pegvisomant on diabetic retinopathy in humans are required [106]. GH has also been implicated, in addition to hyperglycaemia, in the development of diabetic nephropathy [107]. In patients with acromegaly reduced creatinine clearance, microalbuminuria, glomerular basement membrane thickening and mesangial proliferation have been described [108].…”