The Journal of diabetic complications最新文献

Effects of sorbinil, an aldose reductase inhibitor, were examined on renal glomerular structure, urinary albumin and IgG excretion, and vascular albumin permeation in eyes and aorta of 8-month diabetic, galactose-fed, and age-matched control rats. Sorbinil was added to the diet of one-half of the rats in each group at the time of induction of diabetes and galactosemia. Weight gain was impaired in diabetic and galactose-fed rats versus controls and was improved slightly in corresponding sorbinil-treated groups. Plasma glucose and glycosylated hemoglobin levels, food consumption, and 24-hr urine volume were increased in diabetic rats and were unaffected by sorbinil treatment. Food consumption and glycosylated hemoglobin levels were increased in galactose-fed rats, although the increases were smaller than in diabetic rats; glycosylated hemoglobin levels were decreased by sorbinil. Diabetes- and galactosemia-induced increases in albumin permeation in eyes and aorta were prevented by sorbinil. Urinary excretion of albumin and IgG was increased by diabetes and decreased by sorbinil, although differences between the two diabetic groups were not statistically significant for albumin. Galactosemia was associated with an increase in urinary albumin and IgG excretion that did not reach statistical significance. Glomerular capillary basement membrane width (GBMW) was increased in diabetic versus agematched control rats but was unaffected by galactose feeding. GBMW was increased in controls fed sorbinil and glomerular capillary basement membrane thickening in diabetic rats was not prevented by sorbinil. The fractional volume of the glomerulus occupied by mesangium (V_vmes) was increased in diabetic and galactose fed rats versus agematched controls, and was unaffected by sorbinil. The explanation for the discordant effects of sorbinil on generalized vascular dysfunction versus glomerular structural changes remains unclear.

A 30-year-old female with diabetes type 1 of 26 years underwent simultaneous pancreas and kidney transplantation. In spite of good function of both organs she developed a pseudotabetic polyneuropathy of a diabetic type.

To clarify the possible role of intrarenal renin-angiotensin system (RAS) in the evolution of renal hemodynamic alteration in diabetes, we investigated the change of tissue angiotensin-converting enzyme (ACE) activity, a key enzyme of RAS, in the kidneys obtained from streptozotocin-induced diabetic rats. Tissue ACE activity was significantly reduced in both outer cortex (0.29 ± 0.04, mean ± SEM, n = 6) and inner cortex with outer medulla (2.43 ± 0.28, n = 6) of the kidneys from diabetic rats 2 weeks after induction of diabetes compared with those from control rats (0.47 ± 0.05, n = 7, in outer cortex; 3.68 ± 0.32, n = 7, in inner cortex with outer medulla). ACE activities in the lung and aorta of diabetic rats were not different from those of control rats. ACE activities in the serum and urine were significantly elevated in diabetic rats. Treatment of diabetic rats with insulin to achieve near euglycemia completely prevented these alterations in ACE activity, except that, in the urine, the elevation of ACE was partially corrected with insulin. In contrast to ACE activity, activity of N-acetyl-β-D-glucosaminidase (a lysosomal enzyme of the tubule) and r-glutamyl transpeptidase (a brush border enzyme) in the kidney were not reduced in diabetic rats, whereas in the urine both enzyme activities were significantly elevated in diabetic rats. It is likely, therefore, that the reduction of ACE activity in the kidneys of diabetic rats may reflect the impairment of vascular endothelial cells in the kidney, rather than tubular damage. These results suggested that the reduction of tissue ACE activity in the kidneys of diabetic rats might play an important role for the alteration of renal microcirculation and contribute to the development of diabetic nephropathy.

We compared insulin-dependent diabetic outpatients with and without retinopathy for plasma indices of hypothalamo-pituitary-adrenal (HPA) axis activity. Diabetic patients with moderate-to-severe retinopathy had significantly higher postdexamethasone plasma levels of adrenocorticotropic hormone than patients with minimal or no retinopathy. However, when duration of diabetes was taken into account this difference was no longer significant. These data suggest that dysregulation of the HPA axis and retinal microvascular complications found in diabetic patients may both be a function of duration of diabetes.

Medical practitioners often have difficulty in assessing the presence or severity of diabetic retinopathy. The tourniquet test is a method of assessing diabetic capillary fragility that has been felt to reliably correlate with background and proliferative diabetic retinopathy. We studied 100 consecutive diabetic patients and 50 age-matched controls in a masked fashion, using fundus photographs and fluorescein angiography to correlate the amount of capillary fragility with the presence and severity of background and proliferative diabetic retinopathy. Although the severity of diabetic capillary fragility did correlate with the presence and severity of diabetic retinopathy (p < 0.001), this test was not as good an indicator of diabetic retinopathy as were other risk factors such as duration of diabetes (p ⪡ 0.001). The tourniquet test is unreliable in predicting the presence or severity of diabetic retinopathy because of its high false negative response rate.

Little information is available on glucose and energy metabolism in insulin-dependent diabetes mellitus (IDDM) patients receiving immunosuppression after kidney transplantation. We therefore measured insulin sensitivity (euglycemic insulin clamp in combination with indirect calorimetry and infusion of tritiated glucose) in (a) eight steroid-treated IDDM patients after kidney transplantation, (b) ten IDDM patients without nephropathy, (c) ten nondiabetic patients after kidney transplantation, and (d) ten healthy control subjects. Hepatic glucose production was enhanced in both steroid-treated transplanted IDDM patients [4.8 ± 0.6 mg/kg lean body mass (LBM)·min] and IDDM patients without complications (3.8 ± 0.2 mg/kg LBM·min) compared with nondiabetic renal graft recipients and with healthy controls (2.8 ± 0.2 and 2.7 ± 0.1 mg/kg LBM·min; p < 0.01). Insulin-stimulated glucose disposal was reduced in transplanted and non-transplanted IDDM patients and nondiabetic transplanted patients versus healthy controls (6.6 ± 0.8, 5.7 ± 0.7, and 7.5 ± 0.6 versus 9.3 ± 0.6 mg/kg LBM·min; p < 0.05). This reduction was mainly due to an impairment in nonoxidative glucose metabolism, i.e., glycogen synthesis (3.1 ± 0.6, 2.7 ± 0.4, and 3.3 ± 0.5 versus 5.0 ± 0.5 mg/kg LBM·min; p < 0.05 versus healthy controls). It is concluded that IDDM patients without nephropathy show both hepatic and peripheral insulin resistance. In IDDM patients a further increase of insulin resistance caused by treatment with corticosteroids can be corrected by increased insulin doses. However, nondiabetic steroid-treated renal graft recipients show insulin resistance comparable to IDDM patients.