Search PubMed⌕ Search

Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

At least 73 records · Page 4Linked to original sources

Restriction of dietary protein and progression of renal failure in diabetic nephropathy.

In a study of the effect of a low-protein diet on the progression of renal disease 19 insulin-dependent diabetic patients with persistent clinical proteinuria were observed for 12-39 (mean 29) months while they were on a normal-protein diet (1.13 [0.06] g/kg per day), then for 12-49 (mean 33) months on a low-protein diet (0.67 [0.03] g/kg per day). The low-protein diet had no adverse effect on nutrition or glycosylated haemoglobin concentration. Mean supine blood pressure (BP) fell slightly on the low-protein diet and was probably due to the start or modification of antihypertensive medication in 9 patients. The mean rate of decline in glomerular filtration rate fell from 0.61 (SEM 0.14) ml/min per month with the normal-protein diet to 0.14 (0.08) with the low-protein diet, and this effect remained highly significant after adjustment for blood pressure, energy intake, and glycosylated haemoglobin. The rise in the fractional clearance of albumin during a normal-protein diet stopped with the low-protein diet, and there was a significant fall in albumin excretion from 467 (95% CI 234-895) micrograms/24 h on the normal-protein to 340 (138-719) on the low-protein diet. Thus, a low-protein diet, with its reduction in protein and possibly other dietary components such as phosphate or fat, seems to retard the rate of decline of glomerular filtration rate in diabetic nephropathy independently of blood pressure changes and glycaemic control.

Adult↗

Plasma lipid and coagulation factor concentrations in insulin dependent diabetics with microalbuminuria.

OBJECTIVE: To determine whether insulin dependent diabetics with microalbuminuria have significant abnormalities in concentrations of lipoproteins, apolipoproteins AI and B, fibrinogen, and clotting factor VII which could result in increased cardiovascular risk. DESIGN: Case-control study. SETTING: Outpatient department of a metabolic ward. PATIENTS: Group of 20 insulin dependent diabetics with urinary albumin excretion rates greater than 30 micrograms/min (microalbuminuria) and 20 individually matched insulin dependent diabetics with normal urinary albumin excretion rates (below 30 micrograms/min) matched for age, sex, and duration of diabetes. INTERVENTIONS: Fasting venous blood samples were taken for determination of concentrations of glucose, glycated haemoglobin, lipoproteins, apolipoproteins AI and B, fibrinogen, and factor VII. Height, weight, arterial pressure, and usual insulin dose were recorded, and each patient was given a dietary questionnaire to be completed at home. END POINT: Comparison of blood pressure and concentrations of lipoproteins, apolipoproteins AI and B, and fibrinogen in the diabetics with microalbuminuria and the controls. MEASUREMENTS AND MAIN RESULTS: Patients with microalbuminuria had significantly higher concentrations of low density lipoprotein cholesterol (mean 3.33 (SE 0.20) v 2.84 (0.12) mmol/l) and very low density lipoprotein cholesterol (0.30 (0.05) v 0.17 (0.03) mmol/l) than controls but significantly lower concentrations of high density lipoprotein 2 subfraction cholesterol (0.32 (0.04) v 0.54 (0.04) mmol/l). Concentrations of total triglyceride (1.11 (0.14) v 0.68 (0.08) mmol/l), very low density lipoprotein triglyceride (0.56 (0.10) v 0.30 (0.05) mmol/l), apolipoprotein B (0.88 (0.06) v 0.67 (0.03) g/l) and fibrinogen (2.2 (0.1) v 1.9 (0.1) g/l), and diastolic arterial pressure (80 (2) v 74 (2) mm Hg), were also higher in patients with microalbuminuria. CONCLUSIONS: Cardiovascular risk factors--namely, disturbances in lipoprotein and apolipoprotein concentrations, increased fibrinogen concentration, and increased arterial pressure--are already present in insulin dependent diabetics with microalbuminuria. The increased risk of coronary heart disease in patients with clinical proteinuria may result from prolonged exposure to these risk factors, which are present before any impairment of renal function.

Albuminuria↗

Intraocular pressure responses to systemic autonomic stimulation in diabetes mellitus.

The acute changes in intraocular pressure during sustained handgrip contraction (2.5 minutes duration) and the Valsalva manoeuvre (15 seconds duration), both standard tests of autonomic nerve function were studied in 14 diabetic patients and 14 similar aged control subjects. During sustained handgrip contraction, diastolic blood pressure increased by 16.35 +/- 1.87 mmHg in the diabetic patients and 21.36 +/- 0.66 mmHg for the control group. Mean intraocular pressure decreased by 0.71 +/- 0.43 mmHg in the diabetics, p less than 0.05 and 0.64 +/- 0.27 mmHg, p less than 0.01) in the control group. There was no correlation between the blood pressure and the intraocular pressure responses in either group. On release of handgrip contraction, mean recovery intraocular pressure over 5 minutes was significantly lower than mean baseline values for the two groups; control: baseline 14.78 +/- 0.49 to 14.14 +/- 0.67, p less than 0.001 and diabetic: 14.57 +/- 0.65 to 13.86 +/- 0.72, p less than 0.001. During the Valsalva manoeuvre, there was a significant rise in intraocular pressure in the control (+7.85 +/- 0.75 mmHg, p less than 0.001) and the diabetic group (+7.93 +/- 1.18 mmHg, p less than 0.001). 5 minutes after release of intrathoracic pressure, mean recovery intraocular pressure remained significantly below baseline values for the two groups. The Valsalva ratios were in the normal range for the control group (1.21 to 2.2) while 2 diabetics had abnormal ratios.

Autonomic Nervous System↗

Responses of the retinal circulation to systemic autonomic stimulation in diabetes mellitus.

The retinal vessel calibre responses to systemic sympathetic stimulation, were studied in 22 randomly selected diabetic patients (mean age +/- SEM: 54.7 +/- 2.59 years, range 25-73; 13 IDDM, 9 NIDDM; 4 females), using sustained isometric muscle contraction as the stimulus. At a different session the integrity of the autonomic nerve function in these diabetic patients was assessed using 3 standard tests of autonomic nerve function, based on cardiovascular reflexes. Diabetic patients with an intact autonomic nervous system: Group 1, (n = 11, mean age: 54.9 +/- 4.55 years, 7 IDDM 4 NIDDM) showed a mean arteriolar constriction of 9.2% (SEM 2.89, p less than 0.01) and a mean venule constriction of 5.1% (SEM 1.73, p less than 0.02), for a mean rise in diastolic blood pressure of 23.7 mmHg (SEM 2.19 range: 13-33). There were no significant mean retinal vessel responses however, in diabetics with autonomic dysfunction (Group 2): mean arteriolar constriction of 1.2% (SEM 1.38 p greater than 0.05) and venule constriction of 2.1% (SEM 1.38, p greater than 0.05); for a mean rise in diastolic blood pressure of 19.8 mmHg (SEM 4.49, range: 2-50). There was no correlation between the rise in diastolic blood pressure and the retinal arteriolar constriction in the 2 groups (Group 1:r = 0.45, p greater than 0.01 and Group 2: r = 0.56, p greater than 0.05). Duration, type and control of diabetes were not significantly different between the 2 groups. The severity of retinopathy was slightly worse in Group 2 compared to Group 1. These results point to an association between autonomic neuropathy and failure of regulation of retinal blood flow.

Adult↗

Insulin-like growth factor-II in nonislet cell tumors associated with hypoglycemia: increased levels of messenger ribonucleic acid.

The role of insulin-like growth factor-II (IGF-II) in the hypoglycemia associated with nonislet cell tumors is controversial. In this study we have addressed this question by measuring the IGF-II mRNA levels in extracts of these tumors. Hybridization of a 32P-labeled IGF-II cDNA to a Northern blot of RNA from three nonislet cell tumors associated with hypoglycemia (a hemangiopericytoma, fibrosarcoma, and malignant mesenchymal tumor) demonstrated six hybridizing bands, 6.8, 5.6, 4.7, 3.6, 2.6, and 2.1 kilobases in length. These bands were similar to those described by others in a range of tumors and normal tissues. Tissue IGF-II mRNA levels were quantitated using a solution hybridization/RNase protection assay. IGF-II mRNA levels in the tumors were similar to the level present in one line of human hepatoblastoma-derived Hep G2 cells, 5- to 6-fold higher than that in another line of Hep G2 cells, and 2- to 3-fold higher than that in term placenta. In contrast, little or no IGF-II mRNA was detected in a nonfunctioning islet cell adenoma or normal spleen. There was no evidence for amplification of the IGF-II gene in the one tumor in which it was sought. These data suggest that nonislet cell tumors associated with hypoglycemia produce large amounts of IGF-II mRNA and that this IGF-II mRNA appears to be the product of an IGF-II gene, which is apparently normal in the region encoding mature IGF-II peptide.

Adult↗

Microalbuminuria in non-insulin-dependent diabetes: its prevalence in Indian compared with Europid patients.

Non-insulin-dependent diabetes mellitus is strikingly common in British Indians, but their susceptibility to diabetic complications is unknown. The ratio of albumin to creatinine concentrations was measured in samples of the first urine voided in the morning in 154 Indian and 82 Europid patients with non-insulin-dependent diabetes and in a control group of 129 non-diabetic Indians. The ratio was significantly higher in the Indian patients than in the Europid patients and the Indian controls. There were no significant correlations between the logarithm of the albumin: creatinine ratio and age, known duration of diabetes, haemoglobin A1 concentration, or body mass index within either diabetic group. Hypertension and raised albumin:creatinine ratio were significantly associated, and significant correlations were seen between the logarithm of the albumin:creatinine ratio and systolic and diastolic blood pressures in the Indian but not the Europid diabetics. Because of the high prevalence of diabetes at a relatively early age in Indians, nephropathy may emerge as an important clinical problem.

Adult↗

Coronary heart disease and urinary albumin excretion rate in type 2 (non-insulin-dependent) diabetic patients.

Associations between overnight urinary albumin excretion rate and prevalent coronary heart disease and its major risk factors were examined in a cross-sectional study of 141 Type 2 (non-insulin-dependent) diabetic patients. Mean albumin excretion rate was higher in men (geometric mean 13.5 micrograms/min; 95% confidence interval 10.3-17.6) than women (7.5 micrograms/min; 5.7-9.8, p less than 0.01). In diabetic men and women mean albumin excretion rate was higher in those with electrocardiographic and/or symptomatic evidence of coronary heart disease than in those without (men, 23.1 micrograms/min; 95% confidence interval 13.7-39.0 versus 10.6 micrograms/min; 7.9-14.2, p less than 0.01, women, 13.7 micrograms/min; 8.0-23.5 versus 5.4 micrograms/min; 4.2-6.8, p less than 0.01). Multiple logistic regression analysis was used to allow for confounding between variables. In the diabetic group as a whole, raised albumin excretion rate (p less than 0.001), gender (p less than 0.05) and systolic blood pressure (p = 0.06) entered the "best" model for coronary heart disease prediction. In women, albumin excretion rate alone (p less than 0.01) and in men albumin excretion rate (p less than 0.01) and age (p = 0.05) entered the "best" models. We conclude that albumin excretion rate is significantly associated with coronary heart disease morbidity after taking into account the confounding effects of raised blood pressure and other cardiovascular risk factors.

Adult↗

Macrovascular disease in middle-aged diabetic patients in Addis Ababa, Ethiopia.

To define the prevalence of large vessel disease in Ethiopian diabetic patients, the protocol of the World Health Organisation Multinational Study of Vascular disease in Diabetics was used in the Diabetic Clinic of Yekatit 12 Hospital, Addis Ababa: 221 of the possible 261 patients aged 35 to 54 years were examined during 6 months. One hundred seven were diagnosed diabetic 1 to 6 years before study, 74, 7 to 13 years and 40, 14 years or more before the study. Forty-two percent were taking insulin; 18% had retinopathy, 7% heavy albuminuria. Body mass index (BMI) of less than 18 kg/m2 was found in 13.6%; 6.4% of men had BMI more than 27 and 50% of women more than 25. Only 30 patients had ever smoked cigarettes. The plasma cholesterol was less than 6.72 mmol/l in 90% of the 221 patients. Vascular disease led to the diagnosis of diabetes in 3 patients. At study, 19.9% were hypertensive but only 5% at the time of diagnosis. Only 1 patient had had ischaemic gangrene, 1 a stroke, 4 intermittent claudication, 4 angina pectoris and 1 a myocardial infarction. Electrocardiograms, centrally Minnesota-coded in London, were interpreted as Coronary Disease Probable in only 6 patients, and Coronary Disease Possible in 25; the other 190 tracings were normal. It is concluded that macrovascular disease is uncommon in middle-aged Ethiopian diabetic patients in Addis Ababa.

Angina Pectoris↗

The relationship of high density lipoprotein subfractions to alcohol consumption, other lifestyle factors, and coronary heart disease.

Serum high density lipoprotein (HDL) levels are inversely related to the risk of coronary heart disease. Controversy exists regarding the relative importance of HDL subfractions, and few studies have related subfraction levels to lifestyle factors associated with coronary risk. We examined the relationship of the major subfractions, HDL2 and HDL3, to alcohol consumption, cigarette smoking, physical exercise, body mass index, and socioeconomic status in 88 men and 49 women aged 35-64 years. Body mass index was inversely related to HDL2-cholesterol (C), particularly in men, but had no significant relationship with HDL3-C. Cigarette smoking and degree of physical exercise were not significantly related to either HDL subfraction. Alcohol consumption had a strong positive correlation with HDL3-C in both sexes; this association was statistically significant after controlling for cigarette smoking, body mass index, and serum triglyceride. Minnesota-coded ECG abnormalities and positive responses to the WHO chest pain questionnaire were associated with lower levels of HDL-C and HDL2-C in both sexes, and significantly lowered levels of HDL3-C in men but not women. These findings suggest that HDL3-C, as well as HDL2-C, may be related to coronary risk, and indicate that the protective effects of alcohol consumption may be mediated via this subfraction.

Adult↗

Do we need IGI?

Explore the source record for details and available documents.

Diabetes Mellitus↗