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Biomedical subjects

M E Cooper

Publications and source records attributed to M E Cooper.

209 records · Page 12Linked to original sources
PubMedDate not supplied

Lack of effect of gliclazide on early diabetic nephropathy and retinopathy: a two-year controlled study.

This study has attempted to document a specific haemovascular action of gliclazide on the reversal of early diabetic microangiopathy. A prospective double-blind controlled study was performed over 2 years, comparing gliclazide versus placebo in insulin-treated and gliclazide versus glibenclamide in non-insulin-treated diabetic subjects, after a 1-year run-in period. Glycaemic control was not significantly different in gliclazide- and non-gliclazide-treated subjects before or after the commencement of active therapy. Following treatment with gliclazide in 17/32 insulin-treated and 8/17 non-insulin-treated subjects with Albustix-negative proteinuria, there was no difference in retinopathy score, total proteinuria or the renal clearance of creatinine, albumin, transferrin and immunoglobulin G. In the insulin-treated group, progression of retinopathy was observed in approximately one-third of subjects, but no parameter of proteinuria progressed over 2 years. Thus, this study did not detect a reversal of the parameters measured and does not support an action of gliclazide on diabetic microangiopathy, independent of its hypoglycaemic action.

Blood Pressure↗
PubMedDate not supplied

Diabetic vascular complications.

1. Diabetic vascular complications can be arbitrarily divided into micro- and macrovascular complications, the major microvascular complications being nephropathy, retinopathy and neuropathy. Macrovascular complications are due to accelerated atherosclerosis and include ischaemic heart disease, cerebrovascular disease and peripheral vascular disease. 2. It is postulated that metabolic and haemodynamic factors interact leading to the development of diabetic vascular complications. 3. Advanced glycation appears to be an important pathway in the pathogenesis of diabetic complications with evidence that the inhibitor of this process, aminoguanidine, attenuates the development of a range of diabetic vascular complications. 4. The results of experimental studies have led to large-scale clinical trials of various therapeutic agents that act to interfere with the metabolic and haemodynamic pathways implicated in the progression of diabetic complications.

Animals↗
PubMedDate not supplied

Progression of proteinuria in type 1 and type 2 diabetes.

A longitudinal study evaluating the time course of the transition from normal to microalbuminuria, and then on to macroalbuminuria, was made over a mean period of 7 years in a cohort of 52 patients with Type 1 diabetes and 61 patients with Type 2 diabetes. Transient episodes of micro- and macroalbuminuria were often observed before the ultimate development of persistent Albustix-positive proteinuria. The transition from normal to microalbuminuria and from micro- to macroalbuminuria was characterized by rises in renal albumin clearance accompanied by lesser rises in total proteinuria. Seven patients with Type 1 and 12 with Type 2 diabetes showed evidence of progression, the interval for the transition from normal to macroalbuminuria varying from 3 to 5 years. In Type 1 diabetic patients, the development of micro- and macroalbuminuria was associated with a decline in renal function and a rise in systolic blood pressure without a significant change in blood glucose control. In Type 2 diabetic patients, the development of microalbuminuria was associated with a small decline in renal function but no change in blood pressure or blood glucose control. It is concluded that the transition from normal to micro- and on to macroalbuminuria may be more rapid then previously reported and varies considerably among individuals.

Adult↗
PubMedDate not supplied

Microalbuminuria: prognostic and therapeutic implications in diabetes mellitus.

Thirty years following the development of the first radioimmunoassay for albumin, microalbuminuria is widely acknowledged as an important predictor of overt nephropathy in patients with Type 1 diabetes and of cardiovascular mortality in Type 2 diabetes. In addition, there is accumulating evidence to suggest that diabetic patients with microalbuminuria may have more advanced retinopathy, higher blood pressure, and worse dyslipidaemia than patients with normal albumin excretion rates. Recent studies have focused on the role of intervention, principally with antihypertensive therapy and intensive glycaemic control, in reducing microalbuminuria. While successful in reducing urinary albumin excretion it remains to be established whether such therapies will be translated into a reduction in renal failure and decreased cardiovascular morbidity and mortality.

Albuminuria↗
PubMedDate not supplied

Angiotensin-converting enzyme inhibition reduces diabetes-induced vascular hypertrophy: morphometric studies.

Angiotensin-converting enzyme (ACE) activity and vascular mass are both increased in the mesenteric arteries of diabetic rats. As vascular hypertrophy may result from smooth muscle growth following increased formation of angiotensin II, we have examined the histological nature of the increase in mesenteric arterial mass and the role of elevated ACE activity in diabetic vascular hypertrophy by administration of an ACE inhibitor (perindopril). Cross-sectional area of the media was measured in perfusion-fixed mesenteric vessels of diabetic rats 3 weeks after streptozotocin injection. The media was significantly larger (63%) in mesenteric vessels of diabetic rats compared to age-matched control animals. Medial hypertrophy in these vessels was not associated with increased blood pressure or plasma renin activity but there was evidence for increased hemodynamic load due to hyperphagia and intestinal enlargement. Increased mesenteric ACE activity was involved in this process as there was significant inhibition of medial hypertrophy by perindopril. Other markers of cardiovascular hypertrophy such as left ventricular weight and aortic medial area were less affected, but increased in the diabetic group when corrected for significant body weight effects, consistent with a systemic influence of diabetes on cardiovascular mass. These data provide new insights into the mechanisms of vascular complications of diabetes and may have implications for the use of ACE inhibitors in preventing or arresting diabetes-associated vascular pathology.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

The management of diabetic proteinuria. Which antihypertensive agent?

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.

Aged↗
PubMedDate not supplied

Spectrum of proteinuria in type I and type II diabetes.

We prospectively investigated the evolution of proteinuria in 52 type I diabetics over 7.8 +/- 0.3 (mean +/- SE) yr and in 61 type II diabetics over 6.4 +/- 0.3 yr. Measurements of renal protein clearance were performed serially, and the time course of proteinuria was classified in each subject based on a threshold albumin clearance of 11 nl/s, equivalent to a urinary albumin excretion rate of 30 micrograms/min. The classification based on this threshold yielded four distinct patterns of albuminuria: minimal, intermittent, progressing, and established. These patterns occurred in both type I and type II diabetics independently of the duration of follow-up. This study has identified a pattern of intermittent microalbuminuria that is also associated with transient elevations of transferrin and IgG clearances. The relationship of clinical and biochemical parameters to proteinuria patterns was evaluated. No relationship was detected between proteinuria patterns and glycemic control in either type I or type II diabetics. In type I but not type II diabetics, established proteinuria was associated with higher systolic blood pressure and decreased creatinine clearance. The phase of intermittent proteinuria detected in this study may represent a reversible stage in the development of diabetic nephropathy, but the factors that trigger the transition to progressing proteinuria remain obscure.

Adult↗
PubMedDate not supplied

Long-term use of intranasal insulin in insulin-dependent diabetic patients.

This study, in 3 phases, compared the long-term acceptability and efficacy of insulin administered by nasal spray with an intensified subcutaneous regimen in nine type I (insulin-dependent) diabetic subjects on baseline therapy with ultralente insulin. In phase 1, patients were begun and stabilized on a regimen of ultralente daily and Actrapid insulin three times daily. Phase 2 consisted of 4 mo of this intensified subcutaneous regimen. In phase 3, intranasal administration of insulin, with 1% (wt/vol) sodium glycocholate, replaced Actrapid insulin for 4 mo. Glycemic control was compared in each of the three phases. It was possible to maintain the dose of ultralente insulin relatively constant in only six of the nine subjects during the intranasal phase of the study. The six subjects showed a significant rise in glycosylated hemoglobin during the intranasal phase (10.4 +/- 0.6% intranasal vs. 9.1 +/- 0.3% subcutaneous, P less than .05) but not in plasma or urinary glucose levels. There was no significant change in the incidence of hypoglycemic episodes during intranasal insulin therapy in this group. The other three subjects were considered treatment failures. Six of the nine original subjects expressed a preference for intranasal insulin, and one subject complained of mild nasal irritation insufficient to cease treatment. The intranasal route of administration of insulin has the potential to replace short-acting insulin as an adjunct to longer-acting insulin in some insulin-treated diabetic patients.

Administration, Intranasal↗
PubMedDate not supplied

Antihypertensive therapy and diabetic microvascular disease.

Hypertension is commonly associated with diabetes and may represent either a manifestation or a cause of diabetic vascular injury. The following series of studies have explored the role of hypertension in accelerating diabetic microvascular injury. In addition, the role of various classes of antihypertensive agents in preventing or reversing diabetic vascular abnormalities in the presence and absence of systemic hypertension was assessed in both the experimental and clinical context. The induction of streptozotocin diabetes in SHR leads to accelerated development of nephropathy as assessed by both functional and structural parameters. ACE inhibitors but not dihydropyridine calcium channel blockers favourably influence the progression of experimental diabetic nephropathy even in the setting of a normal blood pressure. More recent studies have shown that the trophic changes in the mesenteric arteries from diabetic rats are also attenuated by ACE inhibition. Preliminary results from the Melbourne Diabetic Nephropathy Study Group suggest that the ACE inhibitor, perindopril, is more effective than the dihydropyridine calcium channel blocker, nifedipine, in retarding the rise in urinary albumin excretion in normotensive insulin and noninsulin dependent diabetic patients with microalbuminuria. In conclusion, ACE inhibitors appear to be the drugs of choice in prevention and treatment of diabetic renal disease and may also act as protective agents at other sites of vascular injury.

Albuminuria↗
PubMedDate not supplied

Association between non-right-handedness and cleft lip with or without cleft palate in a Chinese population.

The etiology of non-syndromic cleft lip with or without cleft palate (CL +/- P) is unclear, although both familial and environmental factors are implicated. Because CL +/- P occurs at approximately the time of brain lateralization and is most often unilateral, developmental asymmetry effects have been postulated in CL +/- P etiology. Handedness is frequently used as an indicator of brain lateralization; therefore, several studies have examined the relationship between cleft laterality and handedness. However, these studies have had conflicting results. The present study investigated handedness in a Chinese sample of 211 non-syndromic CL +/- P surgical probands (ascertained in Shanghai for family studies of CL +/- P), 221 population-based but unmatched controls, and 272 first-degree relatives of the probands. Handedness was assessed by means of laterality quotients (LQ) calculated from questionnaire data. Mean LQ's were compared, as were various arbitrary definitions of handedness based on the LQ, for cases versus controls, males versus females, right-sided versus left-sided clefts, and cleft lip alone versus cleft lip plus cleft palate. CL +/- P cases had a significantly higher proportion of non-right-handedness (NRH) than controls, regardless of the definition of NRH (P values < or = .001). There were no statistically significant differences for any of the other comparisons. Familiarity of NRH was tested by comparing first-degree relatives of cases to controls; first-degree relatives were found to have a significantly higher proportion of NRH than controls, supporting familial effects in NRH. These results support the concept of a common etiology and/or developmental pathway for CL +/- P and handedness.

Case-Control Studies↗