Accumulation of Maillard reaction products in skin collagen in diabetes and aging.
Explore the source record for details and available documents.
Aging↗
Biomedical subjects
D R McCance
Publications and source records attributed to D R McCance.
Severe hypercalcaemia four months after acute oliguric renal failure--successful treatment with intravenous clodronate.
A 33 year old man developed acute oliguric failure lasting 66 days, eight days after admission with multiple gun shot wounds. On day 99 after admission, serum calcium was elevated mildly at 2.54 mmol/l (normal range 2.1-2.5 mmol/l). Serum parathormone was undetectable. He was discharged soon afterwards. He presented again on day 164 with nausea, vomiting and blurred vision. Fundoscopy revealed an ischaemic retinopathy and extensive keratopathy. Serum calcium was 3.48 mmol/l and serum creatinine 262 umol/l (normal range 40-110 umol/l). Repeat parathormone was undetectable and there was no evidence of myeloma, sarcoidosis or malignancy. Following treatment with intravenous saline and frusemide, serum calcium fell to a nadir of 3.05 mmol/l. On day 168 an infusion of sodium clodronate 300 mg was given. Twenty-four hours later serum calcium was 2.65 mmol/l and 48 hours later calcium was 2.26 mmol/l. Normocalcaemia was maintained for 17 days and severe hypercalcaemia never recurred. This is the first report in which biphosphonates have been successfully used to treat hypercalcaemia following acute renal failure thus obviating the need for further dialysis.
Acute Kidney Injury↗
Cyclical Cushing's syndrome first diagnosed after pituitary surgery: a trap for the unwary.
Three patients were studied after transsphenoidal microsurgery for Cushing's disease because their symptoms and signs were slow to settle and/or because they had variable endocrine results. All were established as having cyclical Cushing's syndrome, first diagnosed post-operatively. This may be a much more common finding than previously realized and emphasizes the need for detailed and ongoing endocrinological investigation after transsphenoidal surgery for Cushing's disease.
Adult↗
Glomerulonephritis associated with antibodies to neutrophil cytoplasm and glomerular basement membrane.
The prognosis for recovery of renal function of oligoanuric patients with anti-glomerular basement membrane disease is generally regarded as poor. Five patients are reported with dialysis-dependent renal failure in whom antibodies were present simultaneously both to neutrophil cytoplasm and glomerular basement membrane all of whom responded, at least initially, to immunosuppressive therapy and plasma exchange. Two of the 5 remain in clinical and immunological remission at 25 and 51 months of follow-up. We suggest that reversal of dialysis-dependent renal failure may be possible in some patients who display this dual antibody positivity.
Adult↗
The relationship between long-term glycaemic control and diabetic nephropathy.
Urine albumin excretion was studied by two widely accepted methods in 210 patients with insulin-dependent diabetes mellitus and related to the mean of serial glycosylated haemoglobin (HbA1) measurements made every 3 months during the previous 6 years. Microalbuminuria (albumin excretion rate > 20 micrograms/min) was present in 9.5 per cent of patients when defined by a 24-hour collection and 8.1 per cent of patients when defined by a timed overnight urine sample. Those with microalbuminuria, as estimated from a timed overnight urine sample, had a longer duration of diabetes but otherwise did not differ in age, duration of diabetes or arterial blood pressure from patients whose albumin excretion rate was 20 micrograms/min or less irrespective of the method of urine collection. The mean and the most recent HbA1 levels differed significantly between the normal and the microalbuminuric groups when defined by the 24-hour albumin excretion rate (p < 0.001, p < 0.01), but no significant difference between these groups was found when albumin excretion rates were calculated from the timed overnight urine sample. Albumin excretion rate, examined in relation to mean HbA1, increased significantly with worsening glycaemic control whether measured over 24 hours or overnight (p < 0.05, p < 0.01). These findings support an association between glycaemic control and microalbuminuria, but the correlation is weak, dependent on the method of urine collection and is just as good for a relatively short-term as for a long-term measure of average blood glucose.
Adolescent↗
Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen.
N epsilon-(Carboxymethyl)lysine (CML) is formed on oxidative cleavage of carbohydrate adducts to lysine residues in glycated proteins in vitro [Ahmed et al. (1988) J. Biol. Chem. 263, 8816-8821; Dunn et al. (1990) Biochemistry 29, 10964-10970]. We have shown that, in human lens proteins in vivo, the concentration of fructose-lysine (FL), the Amadori adduct of glucose to lysine, is constant with age, while the concentration of the oxidation product, CML, increases significantly with age [Dunn et al. (1989) Biochemistry 28, 9464-9468]. In this work we extend our studies to the analysis of human skin collagen. The extent of glycation of insoluble skin collagen was greater than that of lens proteins (4-6 mmol of FL/mol of lysine in collagen versus 1-2 mmol of FL/mol of lysine in lens proteins), consistent with the lower concentration of glucose in lens, compared to plasma. In contrast to lens, there was a slight but significant age-dependent increase in glycation of skin collagen, 33% between ages 20 and 80. As in lens protein, CML, present at only trace levels in neonatal collagen, increased significantly with age, although the amount of CML in collagen at 80 years of age, approximately 1.5 mmol of CML/mol of lysine, was less than that found in lens protein, approximately 7 mmol of CML/mol of lysine. The concentration of N epsilon-(carboxymethyl)hydroxylysine (CMhL), the product of oxidation of glycated hydroxylysine, also increased with age in collagen, in parallel with the increase in CML, from trace levels at infancy to approximately 5 mmol of CMhL/mol of hydroxylysine at age 80.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Accelerated retinopathy and nephropathy in diabetic pregnancy.
We report a case of severe deterioration in sight despite good metabolic control in a pregnant diabetic patient which has not recovered at two years post-delivery. This was accompanied by a deterioration in renal function which similarly has not improved.
Adult↗
A long-term dose-response study of somatostatin analogue (SMS 201-995, octreotide) in resistant acromegaly.
Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201-995 (octreotide) in active acromegaly. Twenty-four-hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 micrograms three times a day throughout the first month. The dose was increased by 300 micrograms/day at monthly intervals to a maximum of 1500 micrograms/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24-h GH fell from a basal level of 34.3 +/- SEM 7.6 mU/l to 8.0 +/- 1.3 mU/l (P less than 0.05) after 6 months. At 1 month (300 micrograms/day) mean GH was 13.6 +/- 2.2 mU/l and at 2 months (600 micrograms/day) 10.8 +/- 2.2 mU/l (P less than 0.05 vs 300 micrograms/day dose), and at 5 months (1500 micrograms/day) 11.3 +/- 2.0 mU/l (all P less than 0.05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 micrograms/day. After 1 year the mean GH of the group (n = 8) was 7.5 +/- 1.3 mU/l (P less than 0.05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1-year period. We found no evidence that routinely increasing the dose beyond 600 micrograms/day was helpful.
Acromegaly↗
Basal and saline-stimulated plasma atrial natriuretic hormone in Cushing's syndrome.
The pathogenesis of hypertension associated with Cushing's syndrome is incompletely understood. We have studied basal and saline-stimulated levels of plasma atrial natriuretic hormone in 10 subjects with active Cushing's syndrome (8 F: 2 M), aged 43 +/- 4 years (mean +/- SEM). Ten age- and sex-matched normal control subjects were also studied. Subjects fasted from 22.00 h, rose at 07.45 h, and remained ambulant until 09.45 h when blood was taken for plasma ANH, plasma renin activity and serum aldosterone. Subjects then rested supine until 10.00 h when blood was again taken, and blood pressure recorded. Then, while subjects remained supine, 21 of 0.9% NaCl were infused between 10.00 and 14.00 h. Blood was taken hourly. Basal plasma ANH was 8.0 +/- 0.9 pmol/l in Cushing's subjects and 6.9 +/- 2.5 pmol/l in controls. Levels increased in response to saline in both groups, and became significantly higher in the group of patients with Cushing's syndrome (14.00 h level 21.3 +/- 3.9 vs 10.4 +/- 1.9 pmol/l; p less than 0.05). Serum aldosterone and plasma renin activity were not different between groups. Mean blood pressure was higher in patients (114 +/- 4 vs 91 +/- 7 mmHg; p less than 0.05). Urinary sodium excretion was not different between groups before saline, but during the four hours of saline was higher in Cushing's subjects (133 +/- 12 vs 67 +/- 11 mmols; N = 6; p less than 0.05). Our results suggest that during salt loading the exaggerated natriuresis seen in the Cushing's group may have been caused by ANH.
Adult↗
Effect of diabetes and aging on carboxymethyllysine levels in human urine.
Carboxymethyllysine (CML) has been identified as a modified amino acid that accumulates with age in human lens proteins and collagen. CML may be formed by oxidation of fructoselysine (FL), the Amadori adduct formed on nonenzymatic glycosylation of lysine residues in protein, or by reaction of ascorbate with protein under autoxidizing conditions. We proposed that measurements of tissue and urinary CML may be useful as indices of oxidative stress or damage to proteins in vivo. To determine the extent to which oxidation of nonenzymatically glycosylated proteins contributes to urinary CML, we measured the urinary concentrations of FL and CML in diabetic (n = 26) and control (n = 28) patients. The urinary concentration of FL correlated strongly with HbA1 measurements and was significantly higher in diabetic compared with control samples (9.2 +/- 6.5 and 4.0 +/- 2.8 micrograms/mg creatinine, respectively; P less than 0.0001). There was also a strong correlation between the concentrations of CML and FL in both diabetic and control urine (r = 0.67, P less than 0.0001) but only a weakly significant increase in the CML concentration in diabetic compared with control urine (1.2 +/- 0.5 and 1.0 +/- 0.3 micrograms/mg creatinine, respectively; P = 0.05). The molar ratio of CML to FL was significantly lower in diabetic compared with control patients (0.25 +/- 0.12 and 0.43 +/- 0.16, respectively; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Somatostatin analogue (SMS 201-995) in resistant acromegaly: a preliminary report.
The results of treating 10 acromegalic patients with octreotide are compared with those of bromocriptine. Bromocriptine (5 mg 4 times daily for 5 weeks) reduced mean growth hormone (GH) concentrations from 60 to 35 mU/l in 8 patients; a further 2 patients were unable to tolerate this dose. Ten patients (8 unresponsive to bromocriptine) received octreotide 100 micrograms 3 times daily, rising to 500 micrograms 3 times daily according to monthly 24-hour GH profiles. Two patients were withdrawn from octreotide therapy; in the remaining 8, mean GH fell from 36 to 11 mU/l after 6 months' therapy (a reduction to 22% of basal concentrations, compared to a reduction to 58% on bromocriptine). Asymptomatic changes of glucose tolerance and the development of gallstones were noted; further information on the latter is urgently required. In summary, the smallest effective dose of octreotide should be used and each patient should be monitored biochemically.
Acromegaly↗
Plasma atrial natriuretic factor levels during normal pregnancy and pregnancy complicated by diabetes mellitus and hypertension.
Atrial natriuretic factor (ANF) may play a role in the regulation of the changes of blood volume and vascular reactivity during pregnancy and when pregnancy is complicated by hypertension. Reports of plasma ANF levels during pregnancy are conflicting. We have prospectively studied plasma ANF levels during pregnancy in 25 women, and compared these with 20 age-matched non-pregnant women. Five women developed hypertension during pregnancy and a further five who remained normotensive had insulin-dependent diabetes mellitus. Plasma ANF was 6.8 +/- 1.2 (mean +/- SEM) and 6.3 +/- 0.9 pmol/l during weeks 8-15 and 24-31 of normal pregnancy (n = 15; vs non-pregnant levels (4.0 +/- 0.6 pmol/l) P less than 0.05, n = 20). Levels were 4.3 +/- 0.8 and 3.9 +/- 0.4 pmol/l during weeks 16-23 and 32-39. In the diabetic patients and in the group who developed hypertension levels were at no time different from the uncomplicated pregnancy group. Serum aldosterone increased as pregnancy progressed, but plasma renin activity remained unchanged. As plasma ANF was not different between those who did, and those who did not develop hypertension, early measurement of it will not predict who will and who will not develop hypertension during pregnancy.
Adult↗
Long-term glycaemic control and diabetic retinopathy.
216 patients with insulin-dependent diabetes mellitus were studied by retinal photography, and the absence or presence of retinopathy was related to the mean of serial glycosylated haemoglobin measurements (mean HbA1) carried out every 3 months during the previous 6 years. 122 patients had no diabetic retinopathy, 86 had background retinopathy, and 8 proliferative retinopathy. Mean HbA1 levels showed a strong correlation with increasingly severe grades of retinopathy, even when differences in duration of diabetes were taken into account. Proliferative retinopathy was seen only in patients with mean HbA1 above 10%. These results support the view that the development of diabetic retinopathy is related to long-term glycaemic control and emphasise the desirability, and possible benefit, of achieving control as close to normal as is possible for each individual patient.
Adolescent↗
Changes in glucose tolerance and development of gall stones during high dose treatment with octreotide for acromegaly.
Explore the source record for details and available documents.
Acromegaly↗
Are all infants of diabetic mothers "macrosomic".
Explore the source record for details and available documents.
Female↗
Urinary albumin excretion in diabetic pregnancy.
We have analysed the results of urinary albumin excretion in timed overnight urine samples once every two weeks during pregnancy and post-natally in 25 non-diabetic women and 14 women with Type 1 (insulin-dependent) diabetes who were Albustix negative and had urinary albumin excretion less than 15 micrograms.min-1 at conception. Urinary albumin excretion did not vary significantly in the first two trimesters in either group and at 28 weeks was 2.73 micrograms.min-1 (0.32-251.68) (median and range) in the diabetic women and 2.53 micrograms.min-1 (0.90-13.37) in control patients (not significant). During the third trimester urinary albumin excretion increased, and levels were significantly higher in diabetic patients from 36 weeks (9.37 (0.9-31.78) vs 3.52 (0.19-33.74) micrograms.min-1, p less than 0.01) until delivery. In both groups, urinary albumin excretion reached a peak within the week following delivery - diabetic 17.42 micrograms.min-1 (2.03-46.64), control subjects 16.29 micrograms.min-1 (1.53-35.56), but six weeks after delivery, levels were similar to those in early pregnancy. The effect of pregnancy on urinary albumin excretion in these diabetic women would appear to be an exaggeration of the normal pattern, with levels returning to normal post-delivery. It is not possible to know if this has significance for future renal function, but it would be important to investigate this phenomenon in patients who already have raised urinary albumin excretion at conception.
Adult↗
Basal and saline-stimulated levels of plasma atrial natriuretic factor in acromegaly.
We have studied plasma ANF before and after a 4-h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex-matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 +/- 1.5 pmol/l (mean +/- SEM) in acromegalic subjects and 5.3 +/- 0.7 pmol/l in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2-h value, 5.9 +/- 0.9; 4-h value, 5.1 +/- 0.9 pmol/l) but did rise significantly in the control group (2-h value, 8.9 +/- 1.9; 4-h value 9.5 +/- 1.3 pmol/l, both values P less than 0.05 vs basal level). The 4-h ANF value was significantly higher in the control group than in the acromegalic group (P less than 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.
Acromegaly↗
Bilateral inferior petrosal sinus sampling as a routine procedure in ACTH-dependent Cushing's syndrome.
Bilateral inferior petrosal sinus sampling was successfully performed in 12 of 13 consecutive patients with ACTH-dependent Cushing's syndrome. Ten of the patients subsequently had transsphenoidal pituitary microsurgery. Eight patients in whom the inferior petrosal sinus to peripheral vein ACTH level ratio was 1.5 or greater were found to have a pituitary adenoma. One of the remaining two patients who had ratios less than 1.5 had pituitary hyperplasia while the other had no identified abnormality. In five of the patients with pituitary tumour a ratio above 1.5 was present on only one side. Bilateral petrosal sampling is therefore always necessary. Tumour localization within the pituitary was only poorly predicted by either petrosal sinus sampling (four of eight) or computed tomography scanning (three of eight). If petrosal sinus sampling is used early in the differential diagnosis of ACTH-dependent hypercortisolism, then the use of other differential diagnostic tests may not always be necessary.
Adenoma↗