Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes.

Objective: To examine the relationship between plasma plasminogen activator inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes.

Research Design And Methods: We studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers.

The relationship of concentrations of insulin and proinsulin-like molecules with coronary heart disease prevalence and incidence. A study of two ethnic groups.

Objective: To define the potential role of proinsulin-like molecules as risk factors for cardiovascular disease.

Research Design And Methods: Fasting concentrations of proinsulin, des-31,32-proinsulin, and insulin, and of insulin 2 h after a 75-g glucose load, were measured in 1,034 nondiabetic europid subjects and 257 south Asian subjects and related to prevalent coronary heart disease (Minnesota-coded electrocardiographic criteria or ischemic chest pain). In 137 south Asian subjects, the fasting concentrations were related to incident coronary heart disease over a 6.

Gene-environment interaction in the determination of levels of haemostatic variables involved in thrombosis and fibrinolysis.

Functional sequence changes in the promoter of a gene may have a direct effect on the rate of transcription and thus on cellular or plasma levels of the protein. For both the beta fibrinogen gene and the plasminogen activator inhibitor-1 (PAI-1) gene such functional variations have been described. For the fibrinogen gene a G/A sequence variation has been detected at position -455 of the promoter, with carriers of the A allele, representing roughly 20% of the population, consistently having 7-10% higher fibrinogen levels than those with the genotype G/G.

Relationships between plasma leptin and insulin concentrations, but not insulin resistance, in non-insulin-dependent (type 2) diabetes mellitus.

In non-diabetic subjects, insulin concentrations and insulin resistance are clearly connected, and both correlate with leptin levels, making interpretations about mechanisms difficult. In non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), however, insulin concentrations and insulin resistance are less closely associated. Therefore, we examined the relationship of plasma leptin concentrations within insulin resistance and insulin levels in 32 subjects with NIDDM, who underwent measurement of insulin resistance with an insulin sensitivity test.

Investigation of the mechanism underlying the variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia.

The Islington Diabetes Survey identified two groups of non-diabetic individuals, low and high glycators, who remained consistently classified 4.4 +/- 0.2 years after the original study.

Proinsulin-like molecules and plasminogen activator inhibitor type 1 (PAI-1) activity in diabetic and non-diabetic subjects with and without myocardial infarction.

Elevated plasminogen activator inhibitor type 1 (PAI-1) activity has been shown to correlate with plasma insulin, proinsulin-like molecules, serum triglycerides and insulin sensitivity in both non-insulin dependent diabetic (NIDDM) subjects and subjects with coronary heart disease. We examined the relative roles of these variables in determining PAI-1 activity in four groups of male caucasian subjects: non-diabetic subjects with (n = 38) and without (n = 38) previous myocardial infarction (MI) and NIDDM subjects with (n = 26) and without (n = 30) previous MI. Insulin and proinsulin-like molecules were measured using specific two-site immunometric assays and insulin sensitivity estimated using the Homeostasis Model Assessment (HOMA) model.

The Deidesheimer meeting: significance of classical and new risk factors in non-insulin-dependent diabetes mellitus.

The major risk factors appear to explain only a small proportion of the excess risk of coronary heart disease in patients with Non-Insulin-Dependent Diabetes Mellitus (NIDDM). Among novel risk markers that have been-proposed to explain the susceptibility of NIDDM subjects to coronary heart disease are insulin resistance, elevated concentrations of proinsulin-line molecules, plasminogen activator inhibitor, and microalbuminuria. Several prospective studies have shown that hyperinsulinemia predicts coronary heart disease, perhaps independently of established risk factors.

Proteinuria and progressive renal disease: birth weight and microalbuminuria.

Background: Microalbuminuria and nephropathy in diabetic subjects has been linked to low birth weight or short stature in adulthood. We have explored the relationship of foetal growth and intrauterine starvation with microalbuminuria in non-diabetic subjects.

Methods: Albumin excretion rate was measured in an overnight sample in 236 men and women in Preston whose birth anthropometry had been recorded at the local maternity hospital.

Promoter (4G/5G) plasminogen activator inhibitor-1 genotype in Pima Indians: relationship to plasminogen activator inhibitor-1 levels and features of the insulin resistance syndrome.

Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements.

Hyperinsulinaemia, insulin resistance, microalbuminuria and the risk of coronary heart disease.

In population studies both hyperinsulinaemia, a marker for insulin resistance, and microalbuminuria have been shown to predict coronary heart disease. Insulin resistance clusters with several standard cardiovascular risk factors, as well as with abnormalities of fibrinolysis, with small, dense, low-density lipoprotein patterns, and with elevated concentrations of proinsulin-like molecules. This makes the independence of the relationship with coronary heart disease difficult to disentangle.

Non-insulin-dependent diabetes mellitus (NIDDM) in Asians in the UK.

South Asian subjects in the United Kingdom have a substantially increased risk of both diabetes and cardiovascular disease. The excess risk of cardiovascular disease is not explained by risk factors such as smoking, blood pressure or dyslipidaemia. It has been proposed that the insulin resistance syndrome, perhaps consequent upon central obesity, may underlie the risk of both glucose intolerance and cardiovascular disease.

Effect of metformin on intact proinsulin and des 31,32 proinsulin concentrations in subjects with non-insulin-dependent (type 2) diabetes mellitus.

We have investigated the effects of metformin treatment on concentrations of proinsulin-like molecules in subjects with Type 2 (non-insulin-dependent) diabetes mellitus. Metformin was given for 12 weeks in an increasing dose up to 850 mg three times daily in a double-blind placebo-controlled cross-over design to 27 subjects (age 53.0 +/- 9.

Cellular sodium membrane transport and cardiovascular risk factors in non-insulin-dependent diabetes mellitus.

Association have been described between cardiovascular risk factors and abnormalities of both sodium-lithium countertransport (SLC) and sodium-hydrogen ion exchange in subjects with insulin-dependent diabetes mellitus. The data in subjects with non-insulin-dependent diabetes mellitus (NIDDM) are few and more conflicting. This investigation examines erythrocyte SLC rates and platelet sodium-hydrogen ion-exchange kinetics and their relationship to cardiovascular risk factors in 45 nondiabetic and 35 NIDDM white men.

Plasminogen activator inhibitor (PAI-1) and non-insulin-dependent diabetes in Pima Indians, south Asians and Europeans. Populations at varying risk of NIDDM and coronary artery disease.

Activity of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of fibrinolysis, is raised in non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to excess macrovascular disease. We investigated the association of PAI-1 activity with NIDDM in Pima Indians, a racial group with low risk of coronary artery disease, but in whom the impact of NIDDM on the occurrence of coronary artery disease is similar to other racial groups. We studied 308 (136 non-diabetic, 172 diabetic) Pima Indians from Arizona, and 138 (98 non-diabetic, 40 diabetic) South Asians and 129 (80 non-diabetic, 49 diabetic) Europeans living in North London.