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Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

At least 55 records · Page 3Linked to original sources
PubMed1994

Resistance to metabolic actions of insulin and its role in hypertension.

Insulin resistance and hyperinsulinemia have been postulated to be important in raising blood pressure in obese as well as lean hypertensive individuals. However, cause-and-effect relationships among these variables have not been clearly established. The three most widely used methods to assess insulin resistance in vivo (fasting plasma insulin, glucose disposal after a glucose load, or glucose disposal during a hyperinsulinemic euglycemic clamp) may provide different estimates of insulin resistance under various physiological and pathophysiological conditions. Fasting hyperinsulinemia may reflect mainly hepatic insulin resistance, whereas impairment of glucose disposal indicates resistance to the metabolic effects of insulin in skeletal muscle. The importance of these different sites of insulin resistance in the etiology of cardiovascular diseases, however, is still unclear. Although hyperinsulinemia and insulin resistance have been speculated to cause hypertension, most of the evidence supporting this hypothesis has come either from correlation studies or from short-term studies of the cardiovascular, renal, and sympathetic effects of insulin. The few long-term studies that have been conducted in dogs and in humans do not support the insulin concept of hypertension. In fact, these studies suggest that the vasodilator actions of insulin tend to reduce, rather than elevate, blood pressure. Correlations between insulin resistance, hyperinsulinemia, and hypertension do not appear to be explainable by the concept that insulin resistance occurs secondary to hypertension. Obesity may be a key factor in explaining these relationships; weight gain appears to cause insulin resistance, compensatory hyperinsulinemia, and hypertension through parallel, but not necessarily linked, mechanisms. However, insulin resistance and compensatory hyperinsulinemia may contribute to increased risk of other cardiovascular diseases associated with hypertension, such as coronary artery disease.

Animals↗
PubMed1994

The Diabetes Control and Complications Trial (DCCT).

The Diabetes Control and Complications Trial (DCCT) provided much information towards settling the long-running controversy about the effectiveness of improving control of diabetes on the risk of its major complications. With the appearance or the advance of clinically significant retinopathy as its major outcome variable, DCCT randomised 1,441 insulin-dependent diabetic patients to conventional or intensified control groups. In both primary prevention and secondary intervention arms of the trial, intensified control reduced retinopathy risk by half or more, and also reduced nephropathy and neuropathy risks--however, risk of severe hypoglycaemic episodes was increased about three-fold. By contrast, there were no differences in quality of life, neurocognitive or emotional assessments between the two groups. The application of trial findings to 'real life' care is considered.

Adolescent↗
PubMed1993

Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group.

OBJECTIVE: To compare the effects of placebo and GLA on the course of mild diabetic neuropathy over 1 yr. RESEARCH DESIGN AND METHODS: We entered 111 patients with mild diabetic neuropathy from seven centers into a randomized, double-blind, placebo-controlled parallel study of GLA at a dose of 480 mg/day. MNCV, SNAP, CMAP, hot and cold thresholds, sensation, tendon reflexes, and muscle strength were assessed by standard tests in upper and lower limbs. RESULTS: For all 16 parameters, the change over 1 yr in response to GLA was more favorable than the change with placebo, and for 13 parameters, the difference was statistically significant. Sex, age, and type of diabetes did not influence the result, but treatment was more effective in relatively well-controlled than in poorly-controlled diabetic patients. CONCLUSIONS: GLA had a beneficial effect on the course of diabetic neuropathy.

Analysis of Variance↗
PubMed1992

Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria.

Kidney biopsies from 15 type-1 (insulin-dependent) diabetic patients with a range of albumin excretion (AER) were analyzed. Nine patients had normal AER, and six had microalbuminuria. Basement membrane thickness, BMT, and mesangial matrix volume fraction, Vv(mat/glom), were obtained from at least three glomeruli per biopsy. Mesangial structures were estimated with electron microscopic analysis at three levels in each glomerulus. Glomerulopathy parameters were significantly increased in micro- versus normoalbuminuric patients with the following means and (CV): BMT 571 nm (0.12) and 442 nm (0.25), P = 0.03; Vv(mes/glom) 0.31 (0.20) and 0.22 (0.14), P = 0.002; Vv(matrix/glom) 0.17 (0.25) and 0.11 (0.28), P = 0.006; matrix star volume 56 microns 3 (0.47) and 22 microns 3 (0.43), P = 0.02. A positive correlation obtained between AER and each of the glomerulopathy parameters, BM thickness, Vv(mes/glom) and Vv(matrix/glom), as well as between AER and a structural index expressing the sum of changes in the peripheral BM and in the mesangium (r = 0.62, P = 0.01). The results indicated a parallel course of mesangial and peripheral BM changes: a positive correlation obtained between BM thickness and mesangial parameters [BMT versus Vv(matrix/glom): r = 0.82, P = 0.0001] and the ratio of the two subsets of glomerular BM material (PBM:matrix) did not show significant difference between normo- and microalbuminuric groups. The data give strong support to the contention that the transition from normo- into the microalbuminuric phase is linked to progressing glomerulopathy.

Albuminuria↗
PubMed1992

Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study.

A cohort of 63 Type 1 insulin-dependent diabetic patients were first characterized for overnight urinary albumin excretion rate (AER) in 1967. In 1981, seven out of eight (87%) patients with initial AER greater than or equal to 30 less than or equal to 140 micrograms/min (microalbuminuria) developed clinical proteinuria compared to only 2 out of 55 (4%) patients with initial AER less than 30 micrograms/min. The same cohort of patients was reassessed in 1990 after a total follow-up period of 23 years. The aim was to investigate the role of microalbuminuria in the prediction of total/cardiovascular mortality and the development of renal failure, in addition to clinical proteinuria. The initially microalbuminuric patients had a significantly higher risk of developing not only clinical proteinuria (relative risk 9.3, 95% C.I. 1.36 to 3.10, P less than 0.05), but also of dying from a cardiovascular cause (relative risk 2.94, 95% C.I. 1.18 to 7.34, P less than 0.05). The rate of progression to renal failure was higher but not significantly so in the microalbuminuric (2 of 8) compared to the normoalbuminuric (4 of 53) group (relative risk 3.31, 95% C.I. 0.72 to 15.24, NS). In insulin-dependent diabetic patients microalbuminuria is a powerful predictor of clinically overt diabetic renal disease as well as cardiovascular mortality.

Adult↗
PubMed1992

Prospective study of microalbuminuria as predictor of mortality in NIDDM.

Retrospective studies of patients with non-insulin-dependent diabetes mellitus (NIDDM) have suggested that microalbuminuria predicts early all-cause (mainly cardiovascular) mortality independently of arterial blood pressure. These findings have not been confirmed in prospective studies, and it is not known whether the predictive power of microalbuminuria is independent of other major cardiovascular risk factors. During 1985-1987, we examined a representative group of 141 nonproteinuric patients with NIDDM for the prevalence of coronary heart disease and several of its established and putative risk factors, including raised urinary albumin excretion (UAE) rate. Thirty-six patients had microalbuminuria (UAE 20-200 micrograms/min), and 105 had normal UAE (less than 20 micrograms/min). At follow-up, an average of 3.4 yr later, 14 patients had died. There was a highly significant excess mortality (chiefly from cardiovascular disease) among those with microalbuminuria (28%) compared to those without microalbuminuria (4%, P less than 0.001). In univariate survival analysis, significant predictors of all-cause mortality included microalbuminuria (P less than 0.001), hypercholesterolemia (P less than 0.01), hypertriglyceridemia (P less than 0.05), and preexisting coronary heart disease (P less than 0.05). The predictive power of microalbuminuria persisted after adjustment for the effects of other major risk factors (P less than 0.05). We conclude that microalbuminuria is a significant risk marker for mortality in NIDDM, independent of the other risk factors examined. Its presence can be regarded as an index of increased cardiovascular vulnerability and a signal for vigorous efforts at correction of known risk factors.

Albuminuria↗
PubMed1991

Incidence of macrovascular disease in diabetes mellitus: the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics.

We report on the incidence of new macrovascular disease among the 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35-54 years at recruitment) over a mean 8.33 year follow-up period. Overall at the end of the follow-up period the prevalence of macrovascular disease in the cohort was 45%; 43% of the subjects showed evidence of ischaemic heart disease, 4.5% of cerebrovascular disease and 4.2% of peripheral vascular disease. The incidence rates for new disease in those subjects who were free at baseline expressed per 1000 patient years of follow-up were: ischaemic ECG abnormality 23.6 (patients with insulin-dependent diabetes 19.8, patients with non-insulin-dependent diabetes 28.1), myocardial infarction 17.6 (patients with insulin-dependent diabetes 16.5, patients with non-insulin-dependent diabetes 18.8), all ichaemic heart disease 31.7 (patients with insulin-dependent diabetes 30.3, patients with non-insulin-dependent diabetes 33.4), cerebrovascular disease 5.9 and peripheral vascular disease 5.2. Incidence rates were generally similar among men and women except for myocardial infarction in patients with non-insulin-dependent diabetes where men had a significantly higher incidence rate. Macrovascular disease is a major problem in patients with diabetes and in this age group is mainly manifested as ischaemic heart disease.

Adult↗
PubMed1991

Risk factors for macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics.

We have examined the relationship between baseline variables and the incidence of new macrovascular complications amongst the 497 members of the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics over a mean 8.33-year follow-up. In univariate logistic regression analysis the incidence of new ischaemic electrocardiographic abnormality was significantly associated with systolic and diastolic blood pressure, diabetes duration and hypertension in patients with insulin-dependent diabetes, and with smoking in patients with non-insulin-dependent diabetes. New myocardial infarction was associated with systolic blood pressure, plasma cholesterol, proteinuria and smoking in patient with non-insulin-dependent diabetes; there were no significant associations among patients with insulin-dependent diabetes. All new ischaemic heart disease was associated with hypertension in patients with insulin-dependent diabetes, and plasma cholesterol and smoking in patients with non-insulin-dependent diabetes. New cerebrovascular disease was associated with systolic and diastolic blood pressure, ECG abnormality and hypertension. New peripheral vascular disease was associated with smoking. Multivariate analysis showed the following significant associations 1) in patients with insulin-dependent diabetes: ECG abnormality; hypertension, myocardial infarction; smoking, ischaemic heart disease; hypertension, diabetes duration and smoking, 2) in patients with non-insulin-dependent diabetes: ECG abnormality; smoking, myocardial infarction; serum cholesterol, proteinuria and smoking ischaemic heart disease; smoking. For new cerebrovascular disease, proteinuria and ECG abnormality were significant predictors in multivariate analysis. Patients with diabetes share many of the established risk factors for nondiabetic subjects, in addition proteinuria may be of significance in the prediction of macrovascular disease in diabetes.

Adult↗
PubMed1991

Gestational diabetes. Can epidemiology help?

Diagnostic criteria for diabetes mellitus (DM) and impaired glucose tolerance from oral glucose tolerance test results in adults are reviewed in the epidemiological context, highlighting the residual differences between World Health Organization (WHO) and National Diabetes Data Group (NDDG) glycemic criteria with respect to the diagnosis of gestational diabetes. Although the value of the diagnosis of DM (WHO/NDDG criteria) in pregnancy is not called into question, attention is drawn to the paucity of evidence linking lesser degrees of glucose intolerance with significant disturbance of pregnancy outcome when confounding variables such as maternal age, adiposity, and parity are allowed for. It is in the area of the detection and treatment of these lesser degrees of glucose intolerance in pregnancy that serious questions of the detriment-to-benefit ratio arise. A population-based multiethnic multicultural inquiry into diagnostic methodology and criteria in pregnancy is proposed, jointly sponsored by the WHO and the International Diabetes Federation, extending, if possible, to a controlled clinical trial of the effects of intervention.

Blood Glucose↗
PubMed1990

A prospective study of mortality among middle-aged diabetic patients (the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics) I: Causes and death rates.

The 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics have been followed for mortality from 1975 to 1987. During this period 92 patients died. The most common cause of death was myocardial infarction: 36 (39.1%) deaths, heart disease was responsible for 51.1% of deaths and all cardiovascular disease for 55.4%. Neoplastic disease accounted for 25% of the deaths and diabetic nephropathy for 5.4%. Age-standardised mortality rates were higher in men than in women in both Type 1 (insulin-dependent) diabetes and Type 2 (non-insulin-dependent) diabetes. Standardised mortality ratios for the first and second five year follow-up periods were higher for men than for women in Type 2 diabetes but were higher for women than men in Type 1. The results suggest that the female survival advantage seen in the general population may persist in Type 2 but not in Type 1 diabetes.

Adult↗
PubMed1990

A prospective study of mortality among middle-aged diabetic patients (the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: Associated risk factors.

Potential risk factors have been examined for association with mortality over a 10-12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35-54 years at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both sexes with Type 2 (non-insulin-dependent) diabetes mellitus and in women with Type 1 (insulin-dependent) diabetes mellitus; both systolic blood pressure (men) and hypertension (both sexes) (as a categorical variable) are significant in Type 1 diabetes. Hypertension is also significantly associated with all-cause mortality in multivariate analysis in both sexes with Type 1 diabetes as proteinuria is in women with Type 2 diabetes. There is an unexpected negative association between plasma creatinine and all-cause mortality in men with Type 2 diabetes. Systolic blood pressure and hypertension are also significantly linked with cardiovascular mortality in Type 1 diabetes, hypertension having an estimated relative risk of 4.6 [corrected] in multivariate analysis. Serum cholesterol and proteinuria showed the strongest associations with cardiovascular mortality in Type 2 diabetes. Proteinuria is associated with non-cardiovascular mortality in both types of diabetes in univariate but not multivariate analysis. In multivariate analysis hypertension (Type 1 diabetes) and diabetes duration (Type 2 diabetes) are associated with non-cardiovascular mortality. Hypertension and proteinuria have the most consistent associations with mortality in the different analyses with the effect of hypertension appearing stronger in Type 1 diabetes and proteinuria in Type 2 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The clinical and hormonal (C-peptide and glucagon) profile and liability to ketoacidosis during nutritional rehabilitation in Ethiopian patients with malnutrition-related diabetes mellitus.

Cases of malnutrition-related diabetes mellitus conforming to the description of the protein deficient pancreatic diabetes type in Ethiopian patients were compared with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic. Fourteen of 39 malnutrition-related diabetes mellitus patients had fat malabsorption compared with only two of ten Type 1 diabetic patients and one of nine control subjects. Xylose absorption was normal favouring a pancreatic cause for the malabsorption. Plasma C-peptide during oral glucose tolerance test was significantly lower than that in Type 2 diabetic patients and normal control subjects (p less than 0.01 to 0.001) and was also consistently but not significantly higher than in Type 1 diabetic patients. Glucagon secretion patterns were similar in malnutrition-related and Type 1 diabetic patients. Of 23 new malnutrition-related diabetic patients treated with glibenclamide after nutritional rehabilitation and insulin treatment, only three responded, 14 were unresponsive but remained ketosis free for over eight days while another six developed ketoacidosis or significant ketonuria within two to six days during the trial. Sixteen unselected Type 1 diabetic patients who discontinued their insulin therapy all developed frank ketoacidosis after a mean of 5.5 days. The similarity of the malnutrition-related and Type 1 diabetes mellitus in age of onset, insulin requirement for diabetic control and appearance of ketosis-proneness in some cases, together with the similarity of C-peptide and glucagon secretion patterns suggest that the protein deficient pancreatic diabetes variant of malnutrition-related diabetes mellitus may be Type 1 diabetes mellitus modified by the background of malnutrition rather than an aetiologically separate entity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Impaired autoregulation of the retinal vasculature and microalbuminuria in diabetes mellitus.

The relationship between microalbuminuria and retinal vessel responses to sustained handgrip contraction was studied in a group of 20 diabetic patients. The diabetics were divided into two groups based on their albumin excretion rates (AER): Group 1 (AER less than or equal to 10 mcg/min) consisted of ten diabetic patients, mean age 55.8 +/- 3.9 years (mean +/- SEM); five IDDM and five NIDDM. Group 2 (AER greater than 10 mcg/min) comprised ten diabetic patients: mean age 56.8 +/- 3.04 years; six IDDM and four NIDDM. Both groups were similar in that there were no significant differences between mean age, type of diabetes, mean duration of diabetes, glycaemic control or mean resting blood pressures. Group 2 diabetics had a higher incidence of autonomic dysfunction than Group 1, based on the results of four standard tests of autonomic nerve function. There were significantly decreased retinal vessel responses to sustained handgrip contraction in Group 2 diabetics (mean arteriolar constriction 0.1 +/- 0.32%, and mean venule constriction 1.0% +/- 0.99%) compared with Group 1 diabetics (mean arteriolar constriction 6.9 +/- 1.69%, and mean venule constriction 4.2 +/- 0.05%). Retinopathy was slightly worse in Group 2. The implications of the association of microalbuminuria (AER greater than 10 mcg/min) and loss of retinal vessel reactivity to sustained handgrip contraction are discussed.

Adult↗