Prediabetes is a condition when the blood glucose levels are above the normal range but below the threshold for defining diabetes. Previously considered benign, it is now recognized to be associated with various macrovascular and microvascular complications, with increases in the risk of cardiovascular events, nephropathy neuropathy, and retinopathy. Early identification of prediabetics may help detect the risk for these future complications at an earlier stage. Moreover, therapeutic options for prediabetes are available, which can retard its progression to diabetes and the subsequent development of complications. Hence, we make a case for the early identification of prediabetes through screening methods and appropriate institution of management strategies.

Diabetes mellitus (DM) is a known risk factor for severe coronavirus disease 2019 (COVID-19), but the clinical impact of undiagnosed diabetes and prediabetes in COVID-19 are unclear particularly in Japan. We clarify the difference in clinical characteristics, including age, sex, body mass index and co-morbidities, laboratory findings and critical outcomes, in a large Japanese COVID-19 cohort without diabetes, with prediabetes, undiagnosed diabetes and diagnosed diabetes, and to identify associated risk factors.

This multicentre, retrospective cohort study used the Japan COVID-19 Task Force database, which included data on 2430 hospitalized COVID-19 patients from over 70 hospitals from February 2020 to October 2021. The prevalence of prediabetes, undiagnosed diabetes and diagnosed diabetes were estimated based on HbA1c levels or a clinical diabetes history. Critical outcomes were defined as the use of high-flow oxygen, invasive positive-pressure ventilation or extracorporeal membrane oxygenation, or death during hospitalization.

Prediabetes, undiagnosed diabetes and diagnosed diabetes were observed in 40.9%, 10.0% and 23.0%, respectively. Similar to diagnosed diabetes, prediabetes and undiagnosed diabetes were risk factors for critical COVID-19 outcomes (adjusted odds ratio [aOR] [95% CI]: 2.13 [1.31-3.48] and 4.00 [2.19-7.28], respectively). HbA1c was associated with COVID-19 severity in prediabetes patients (aOR [95% CI]: 11.2 [3.49-36.3]), but not other groups.

We documented the clinical characteristics and outcomes of Japanese COVID-19 patients according to HbA1c levels or diabetes co-morbidity. As well as undiagnosed and diagnosed diabetes, physicians should be aware of prediabetes related to COVID-19 severity.

Previous clinical studies have shown that various measures of glucose metabolism are associated with a risk of chronic kidney disease in different populations, but results were not consistent. In this study we assessed measures of glucose metabolism and their association with kidney function in a population-based study.

The Netherlands Epidemiology of Obesity study is a population-based cohort study of middle-aged men and women. We categorized the study population according to glycaemic levels into normoglycaemia (reference group), pre-diabetes mellitus (pre-DM), known DM and newly diagnosed DM. Outcome variables were serum creatinine, estimated glomerular filtration rate (eGFR), glomerular hyperfiltration (defined as an eGFR >90th percentile; >102 mL/min/1.73 m2) and micro-albuminuria. We examined the association between measures of glucose metabolism [fasting glucose, haemoglobin A1c (HbA1c), fasting insulin, glucose area under the curve (AUC), insulin AUC, Homoeostatic Model Assessment of Insulin Resistance (HOMA-IR), HOMA of β-cell function (HOMA-B) and disposition index] and measures of kidney function.

Of the total population (N = 6338), 55% of participants were classified as normoglycaemic (reference), 35% as pre-DM, 7% as DM and 4% as newly diagnosed DM. Compared with the reference group, diagnosed and newly diagnosed DMs were associated with a slightly higher trend in eGFR {+2.1 mL/min/1.73 m2 [95% confidence interval (CI) -0.2-4.4] and +2.7 mL/min/1.73 m2 [95% CI -0.3-5.7], respectively}. A 1% higher HbA1c was associated with increased odds of hyperfiltration [odds ratio (OR) 1.41 (95% CI 1.06-1.88)]. Higher levels of fasting plasma glucose, AUC glucose and HOMA-B were associated with hyperfiltration. Fasting insulin, AUC insulin and HOMA-IR were not associated with hyperfiltration. The OR of microalbuminuria was 1.21 (95% CI 1.04-1.42) per mmol/L higher fasting glucose concentrations.

Both fasting and post-prandial glucose and HOMA-B, but not measures of insulin resistance, were associated with glomerular hyperfiltration, while fasting glucose was also associated with microalbuminuria.

This systematic review and meta-analysis aims to find the effect of Gymnema sylvestre (GS) supplementation on glycemic control in type-2 diabetes mellitus (T2DM). PubMed, Cochrane library, Google Scholar, and Science Direct were searched from inception to June 2020 to identify the studies that reported GS supplementation on glycemic parameters. Standardized mean difference (SMD) was calculated by comparing the post-intervention data with baseline data. SMDs with 95% confidence intervals (CIs) were pooled using a random-effects model. Our meta-analysis consisting of 10 studies with a total of 419 participants showed that GS supplementation significantly reduces fasting blood glucose (FBG) (SMD 1.57 mg/dl, 95% CI 2.22 to -0.93, p < .0001, I² 90%), postprandial blood glucose (PPBG) (SMD 1.04 mg/dl, 95% CI 1.53 to -0.54, p < .0001, I² 80%), and glycated haemoglobin (HbA1c) (SMD 3.91, 95% CI 7.35 to -0.16%, p < .0001, I² 99%) compared to baseline. Further, our study also found that GS significantly reduces triglycerides (SMD 1.81 mg/dl, 95% CI 2.95 to -0.66, p < .0001, I² : 96%), and total cholesterol (SMD 4.10 mg/dl, 95% CI 7.21 to -0.99, p < .0001, I² : 98%) compared to baseline. Our study shows that GS supplementation is effective in improving glycemic control and reducing lipid levels in T2DM patients and suggests that such supplementation might be used as an effective therapy for the management of T2DM and its associated complications to an extent.

We aimed to investigate changes in renal cortical stiffness (CS) in Type 2 diabetes mellitus (DM) and pre-DM patients compared to subjects with normal glucose metabolism (NGM), as well as the usefulness of renal CS to determine the presence of nephropathy.

This study included 125 individuals with NGM, pre-DM and Type 2 DM. Routine laboratory data was obtained, and micro- and macrovascular involvement were investigated. Urinary albumin-creatinine ratio (UACR) was measured for urinary albuminuria detection. In addition to routine renal ultrasonography, CS was measured using renal elastography.

Among the included patients, 42, 40 and 43 patients had NGM, pre-DM and Type 2 DM, respectively, with prevalence of nephropathy of 5%, 15% and 33%, respectively. Carotid and aortic intima-media thickness (IMT), renal width, and CS were found to be higher in the pre-DM and Type 2 DM groups than the NGM group. Aortic IMT, renal width and UACR levels were independently associated with CS. Patients with nephropathy were found to have a higher CS value than those without nephropathy (8.72 ± 1.67 kPa vs. 10.60 ± 1.74 kPa, p = 0.001). In receiver operating characteristic curve analysis, when the cut-off value for CS was taken as 9.2 kPa, renal CS predicted the possibility of nephropathy with 78.9% sensitivity and 71.4% specificity.

CS values are significantly higher in patients with impaired glucose metabolism. We recommend CS measurement as part of routine screening of nephropathy in patients with pre-DM and newly diagnosed Type 2 DM.

Despite our understanding of diabetes as an established risk factor for progressive kidney disease and cardiac complications, the prognostic significance of prediabetes in patients with chronic kidney disease (CKD) remains largely unknown.

Participants of the Chronic Renal Insufficiency Cohort (CRIC) were categorized as having normoglycemia, prediabetes, or diabetes according to fasting plasma glucose, glycated hemoglobin A1c (HbA1c), and treatment with antidiabetic drugs at baseline. Unadjusted and adjusted proportional hazards models were fit to estimate the association of prediabetes and diabetes (versus normoglycemia) with: (1) composite renal outcome (end-stage renal disease, 50% decline in estimated glomerular filtration rate to ≤ 15 mL/min/1.73 m2, or doubling of urine protein-to-creatinine ratio to ≥ 0.22 g/g creatinine); (2) composite cardiovascular (CV) outcome (congestive heart failure, myocardial infarction or stroke); and (3) all-cause mortality.

Of the 3701 individuals analyzed, 945 were normoglycemic, 847 had prediabetes and 1909 had diabetes. The median follow-up was 7.5 years. Prediabetes was not associated with the composite renal outcome (adjusted hazard ratio [aHR] 1.13; 95% confidence interval [CI], 0.96-1.32; P = 0.14), but was associated with proteinuria progression (aHR 1.23; 95% CI, 1.03-1.47; P = 0.02). Prediabetes was associated with a higher risk of the composite CV outcome (aHR 1.38; 95% CI, 1.05-1.82; P = 0.02) and a trend towards all-cause mortality (aHR 1.28; 95% CI, 0.99-1.66; P = 0.07). Participants with diabetes had an increased risk of the composite renal outcome, the composite CV outcome, and all-cause mortality.

In individuals with CKD, prediabetes was not associated with composite renal outcome, but was associated with an increased risk of proteinuria progression and adverse CV outcomes.

Investing in women's health is an inevitable investment in our future. We systematically reviewed the available evidence and summarized the weighted prevalence of type 2 diabetes (T2DM) and pre-diabetes mellitus (pre-DM) in women of childbearing age (15-49 years) in the Middle East and North African (MENA) region.

We comprehensively searched six electronic databases to retrieve published literature and prevalence studies on T2DM and pre-DM in women of childbearing age in the MENA. Retrieved citations were screened and data were extracted by at least two independent reviewers. Weighted T2DM and pre-DM prevalence was estimated using the random-effects model.

Of the 10,010 screened citations, 48 research reports were eligible. Respectively, 46 and 24 research reports on T2DM and pre-DM prevalence estimates, from 14 and 10 countries, were included. Overall, the weighted T2DM and pre-DM prevalence in 14 and 10 MENA countries, respectively, were 7.5% (95% confidence interval [CI], 6.1-9.0) and 7.6% (95% CI, 5.2-10.4). In women sampled from general populations, T2DM prevalence ranged from 0.0 to 35.2% (pooled, 7.7%; 95% CI, 6.1-9.4%) and pre-DM prevalence ranged from 0.0 to 40.0% (pooled, 7.9%; 95% CI, 5.3-11.0%). T2DM was more common in the Fertile Crescent countries (10.7%, 95% CI, 5.2-17.7%), followed by the Arab Peninsula countries (7.6%, 95% CI, 5.9-9.5%) and North African countries and Iran (6.5%, 95% CI, 4.3-9.1%). Pre-DM prevalence was highest in the Fertile Crescent countries (22.7%, 95% CI, 14.2-32.4%), followed by the Arab Peninsula countries (8.6%, 95% CI, 5.5-12.1%) and North Africa and Iran (3.3%, 95% CI, 1.0-6.7%).

T2DM and pre-DM are common in women of childbearing age in MENA countries. The high DM burden in this vital population group could lead to adverse pregnancy outcomes and acceleration of the intergenerational risk of DM. Our review presented data and highlighted gaps in the evidence of the DM burden in women of childbearing age, to inform policy-makers and researchers.

PROSPERO CRD42017069231.

Diabetes mellitus is a risk factor for the development and progression of chronic kidney disease (CKD). However, the association of prediabetes with adverse kidney outcomes is uncertain.

We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), including 9,361 participants without diabetes at baseline. We categorized participants according to fasting glucose as having impaired fasting glucose (≥100 mg/dL [(≥5.6 mmol/L]) or normoglycemia (<100 mg/dL [(<5.6 mmol/L]). Unadjusted and adjusted proportional hazards models were fit to estimate the association of impaired fasting glucose (versus normoglycemia) with a composite outcome of worsening kidney function (≥30% decrease in eGFR to <60 ml/min/1.73 m2 in participants without baseline CKD; ≥50% decrease in eGFR or need of long-term dialysis/kidney transplantation in participants with CKD) or incident albuminuria (doubling of urinary albumin to creatinine ratio from <10 mg/g to >10 mg/g). These outcomes were also evaluated separately, and according to CKD status at baseline.

The mean age was 67.9 ± 9.4 years, 35.5% were female, and 31.4% were black. The median follow-up was 3.3 years and 41.8% had impaired fasting glucose. Impaired fasting glucose was not associated with higher rates of the composite outcome (HR 0.97; 95%CI 0.81-1.16), worsening kidney function (HR 1.02; 95%CI 0.75-1.37), or albuminuria (HR 0.98; 95%CI 0.78-1.23). Similarly, there was no association of impaired fasting glucose with outcomes according to baseline CKD status.

Impaired fasting glucose at baseline was not associated with the development of worsening kidney function or albuminuria in participants of SPRINT.

Diabetes mellitus is a non-communicable metabolic derangement afflicting several millions of individuals globally. It is associated with several micro and macrovascular complications and is also a leading cause of mortality. The unresolved issue is that of definition of the diagnostic threshold for diabetes. The World Health Organization and the American Diabetes Association (ADA) have laid down several diagnostic criteria for diagnosing diabetes and prediabetes based on the accumulating body of evidence.This review has attempted to analyse the scientific evidence supporting the justification of these differing criteria. The evidence for diagnosing diabetes is strong, and there is a concordance between the two professional bodies. The controversy arises when describing the normal lower limit of fasting plasma glucose (FPG) with little evidence favouring the reduction of the FPG by the ADA. Several studies have also shown the development of complications specific for diabetes in patients with prediabetes as defined by the current criteria though there is a significant overlap of such prevalence in individuals with normoglycemia. Large multinational longitudinal prospective studies involving subjects without diabetes and retinopathy at baseline will ideally help identify the threshold of glycemic measurements for future development of diabetes and its complications.

Previous clinical studies have shown that the circulating level of endostatin is related to kidney injury. We hypothesized that the impact of HbA1c, fasting, and postprandial plasma glucose on urinary albumin excretion would be related to the serum endostatin level.

A cross-sectional, community-based population study of 1057 Japanese residents was conducted. Of these subjects, 162 with a fasting plasma glucose value between 5.5 and 6.9 mmol/L and an HbA1c level of <6.5 % received an oral glucose tolerance test, had serum endostatin measured, and had the urinary albumin/creatinine ratio (UACR) calculated.

In multivariate analysis, 2-h postprandial plasma glucose (β = 0.26, P < 0.01) was significantly associated with log-transformed UACR, independently of fasting plasma glucose (β = 0.14, P = 0.28) and HbA1c (β = -0.08, P = 0.57). When divided by the median value of endostatin (82.2 ng/mL), 2-h postprandial plasma glucose (β = 0.38, P = 0.01) remained significantly associated with the log-transformed UACR of the participants below the median, while the fasting plasma glucose (β = 0.34, P = 0.046) was independently associated with the log-transformed UACR of participants above the median.

Postprandial plasma glucose was independently associated with the urinary albumin excretion of the residents with prediabetes. Moreover, this relationship was limited to residents with a serum endostatin level below the median.

We investigated the prevalence of albuminuria across a range of fasting plasma glucose (FPG), including normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetes.

A total of 5202 subjects who participated in the fifth Korea National Health and Nutrition Examination Survey were enrolled. Spot urine samples were taken and the albumin-creatinine ratio was calculated for each patient. Subjects were divided into five groups according to FPG levels: <5.0 (NFG1, n=1,905), 5.0-5.5 (NFG2, n=1,784), 5.6-6.0 (IFG1, n=727), 6.1-6.9 (IFG2, n=268), and ≥7.0 (diabetes, n=518) mmol/L. Analysis of covariance tests and logistic regression were used.

The rates of albuminuria were 4.1%, 6.0%, 7.6%, 12.3%, and 23.4% in the NFG1, NFG2, IFG1, IFG2 and diabetes groups, respectively (P<0.01 for the trend). The rate of albuminuria in the IFG2 group was significantly higher than in the IFG1 group, even after adjustment for age, gender, hypertension, and obesity. The odds ratio for the presence of albuminuria in the IFG2 group was 1.87 (95% CI, 1.19-2.94), using the NFG1 group as a control in logistic regression analyses.

Albuminuria is more prevalent in subjects in the higher range of IFG. Therefore, strategies to reduce albuminuria should be emphasized especially in these subjects.

Prediabetes (intermediate hyperglycaemia) is a high-risk state for diabetes that is defined by glycaemic variables that are higher than normal, but lower than diabetes thresholds. 5-10% of people per year with prediabetes will progress to diabetes, with the same proportion converting back to normoglycaemia. Prevalence of prediabetes is increasing worldwide and experts have projected that more than 470 million people will have prediabetes by 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction-abnormalities that start before glucose changes are detectable. Observational evidence shows associations between prediabetes and early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores using non-invasive measures and blood-based metabolic traits, in addition to glycaemic values, could optimise estimation of diabetes risk. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of a 40-70% relative-risk reduction. Accumulating data also show potential benefits from pharmacotherapy.

To evaluate the importance of oral glucose tolerance test (OGTT) in predicting diabetes and cardiovascular disease in patients with and without Metabolic Syndrome from a population treated in a primary care unit.

A prospective cohort study was conducted with subjects regularly attending the primary care unit of Hospital de Clínicas de Porto Alegre. Participants underwent a 75 g OGTT. Metabolic syndrome definition was based on the criteria of IDF/AHA/NHLBI-2010.

Participants mean age was 61 ± 12 years (males: 38%; whites: 67%). Of the 148 subjects included, 127 (86%) were followed for 36 ± 14 months, 21 (14%) were lost. Subjects were classified into four groups based on baseline OGTT: 29% normal (n = 43), 28% impaired fasting glucose (IFG; n = 42), 26% impaired glucose tolerance (IGT; n = 38), and 17% diabetes (n = 25). Metabolic syndrome prevalence was lower in normal group (28%), intermediate in IFG (62%) and IGT (65%) groups, and higher among subjects with diabetes (92%; P <0.001). Incidence of diabetes increased along with the stages of glucose metabolism disturbance (normal: 0%, IFG: 16%, IGT: 28%; P = 0.004). No patient with normal OGTT developed diabetes, regardless metabolic syndrome presence. Diabetes at baseline was the major determinant of cardiovascular disease occurrence (normal: 0%, IFG: 4%, IGT: 0%, diabetes: 24%; P = 0.001). In Cox-regression analysis, only the 2 h OGTT results were associated with diabetes (OR = 1.03; 95%CI 1.01-1.06; P <0.001) and cardiovascular disease development (OR = 1.013; 95%CI 1.002-1.025; P = 0.024).

In this sample of subjects undergoing diabetes screening, the OGTT predicted diabetes and cardiovascular disease more effectively than the metabolic syndrome status.

Chronic idiopathic axonal polyneuropathy (CIAP) is referred to as axonal neuropathy after an adequate workup fails to determine a cause. A subgroup of patients with CIAP has impaired glucose tolerance (IGT). These patients have been considered by some investigators to have a neuropathy as a result of IGT and/or metabolic syndrome (MetS). Patients with CIAP usually suffer from chronic pain and associated depression, both of which have been proposed to cause insulin resistance (IR) by such mechanisms as a sustained increase in the corticosteroids and catecholamines, and chronic low grade inflammation. In a pilot study of 14 patients with CIAP+IGT and eight normal controls, we found a correlation between the number of features of the MetS with scores of pain and depression. There was no increase in the frequency of retinopathy and nephropathy in these patients, contrary to what would have been expected if chronic hyperglycemia was the cause of the neuropathy. We hypothesize that neuropathy has an unclear cause in the majority of patients with CIAP+IGT/MetS--and IGT/MetS are a result of comorbidities of CIAP, including chronic pain and depression.

Asian ethnicity is said to be a risk factor for microalbuminuria. Prevalence studies in native Asians, especially Indians, are scarce. The aim was to study the prevalence of microalbuminuria in patients with type 2 diabetes mellitus and to identify the associated risk factors.

Eight hundred consecutive patients attending the endocrine outpatient clinic were screened. Six hundred seventy patients were eligible for microalbuminuria screening. Urinalysis was done in a random spot urine sample using dipsticks. History, physical examination, and metabolic data were recorded.

The mean age and body mass index of the study population were 52.13 +/- 9.9 years and 26.19 +/- 4.34 kg/m(2), respectively. The median duration of diabetes was 5 years. Microalbuminuria was found in 25.5% (95% confidence interval, 22.4-29%) and macroproteinuria in 16.2% (95% confidence interval, 13.5-19.1%). In patients with duration of diabetes less than 1 year, the prevalence of microalbuminuria was 24.7%, and that of macroproteinuria was 6.2%. The risk factors associated with microalbuminuria and macroproteinuria were glycated hemoglobin, retinopathy, and calcium channel blocker intake. However, waist circumference was negatively associated with macroproteinuria but not with microalbuminuria. This difference in the risk factors supports the newer concept that microalbuminuria and diabetic nephropathy are pathophysiologically different and may not be inextricably linked.

The high proportion of patients who present with albuminuria within the first year of diagnosis probably indicates longer duration of prior undiagnosed diabetes. Screening for asymptomatic diabetes and defining newer risk factors to identify those at risk for complications are essential to reduce the socioeconomic burden of diabetes.

Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality. The effect of nicorandil on proteinuria in hypertensive patients well controlled by antihypertensive agents containing a low dose of valsartan has not been studied.

A total of 136 proteinuric (300-3000 mg/day), valsartan-treated hypertensive patients with blood pressure less than 140/90 mmHg were randomized into three groups to receive placebo, isosorbide dinitrate (30 mg/day), or nicorandil (15 mg/day) for 6 months.

The average dose of valsartan given to the patients was similar in the three groups. Creatinine clearance remained stable throughout the study in the three groups. Nicorandil, but not isosorbide dinitrate, significantly reduced proteinuria by 44% after 6 months (P < 0.0001). Urinary endothelin-1 levels significantly decreased after administration of nicorandil (P = 0.002), whereas placebo and isosorbide dinitrate had no effect. Urinary excretion of endothelin-1 was significantly correlated with improvement in urinary protein excretion in nicorandil-treated patients (r = 0.69, P < 0.0001). The urinary excretion of retinol-binding protein decreased after nicorandil administration, probably reflecting an improvement in tubular function. In contrast, the urinary excretion of immunoglobulin G did not change significantly throughout the study in the three groups. Multivariate analysis revealed that proteinuria was only significantly correlated with the use of nicorandil (model adjusted r = 0.35, P < 0.0001).

The addition of nicorandil to treatment for patients with well controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and nitric oxide effects, possibly through inhibiting renal endothelin-1 synthesis and improving tubular function.

Peripheral neuropathy is common. Diabetes is the most common cause, accounting for approximately half of cases, but up to 1/3rd of neuropathy patients have no identifiable etiology. Among this population, impaired glucose tolerance (IGT or "prediabetes") is observed in approximately 40%. The exact nature of the relationship between IGT and neuropathy is debated.

A variety of evidence suggests IGT causes neuropathy. Neuropathy may occur early in diabetes. The neuropathy associated with IGT is clinically similar to early diabetic neuropathy, with preferential injury to small nerve fibers resulting in pain and autonomic dysfunction. IGT and diabetic neuropathy patients share abnormal microvascular endothelial dysfunction. Treatment of IGT subjects with diet and exercise reduces risk of progression to diabetes, and those with neuropathy experience a short-term improvement in small fiber function with sustained benefit for pain. An evolving literature links other aspects of the metabolic syndrome to peripheral neuropathy.

IGT is common in peripheral neuropathy patients. The extent to which IGT directly causes nerve injury as opposed to being a covariant with other equally or more important features (eg, obesity, metabolic syndrome) remains to be determined. Preliminary data suggest diet and exercise counseling may be a useful treatment strategy.

The aim of the present study was to examine the influence of urinary flow rate on markers of renal function in children. A sub-study of the New England Children's Amalgam Trial collected 82 pairs of urine samples from children aged 10-16 years: a timed overnight collection and a spot daytime sample collected the following day. These samples were analyzed for albumin, gamma-glutamyl transpeptidase (gamma-GT), N-acetyl-beta-D-glucosaminidase (NAG), alpha1-microglobulin (A1M), and creatinine concentration. Regression analysis was used to model the effect of urinary flow rate in the timed overnight samples. A paired t-test compared concentrations and creatinine-corrected renal markers between overnight and daytime samples. Albumin, gamma-GT, NAG, and A1M excretion rates increased significantly with urinary flow rate. Their corresponding creatinine-corrected markers did not vary significantly with urinary flow rate, but the creatinine-corrected excretions of albumin, gamma-GT, and NAG were significantly higher in daytime samples than in overnight samples, with the same (non-significant) trend for A1M. The influence of urinary flow rate on creatinine-corrected markers of renal function was markedly less than its influence on excretion rates. Therefore, the use of creatinine-corrected markers seems to be a good choice in practice, with the caveat that daytime and overnight samples are not comparable.

The aim of this study is to examine the effects of age, sex, and race on the excretion and concentrations of albumin, gamma-glutamyl transpeptidase (gamma-GT), N-acetyl-beta-d-glucosaminidase (NAG), alpha(1)-microglobulin (alpha1M), and creatinine in children.

Secondary analysis of a clinical trial, The New England Children's Amalgam Trial, which examined effects of amalgam dental fillings.

534 children aged 6 to 10 years at baseline were recruited from Boston, MA, and rural Maine.

Age, sex, and race.

Urine samples were collected annually for 5 years and analyzed for creatinine, albumin, gamma-GT, NAG, and alpha1M concentrations. Repeated-measures analysis of covariance was used to model effects of age, sex, and race on these values, as well as calculated excretion rates.

All measures of creatinine and gamma-GT increased significantly with age. Albumin and gamma-GT concentration and excretion (milligrams per gram of creatinine or units per gram creatinine) were significantly greater for girls compared with boys. alpha1M concentration and creatinine excretion were greater for boys compared with girls. Creatinine concentration was significantly greater for blacks than for whites and Hispanics. Creatinine excretion and all gamma-GT levels were significantly greater for blacks and Hispanics compared with non-Hispanic whites.

The study population, recruited for a clinical trial, was of lower socioeconomic status than the general population. The high limit of detection for alpha1M resulted in a majority of samples less than the detection limit.

We recommend considering age, sex, and race in the interpretation of urinary markers. It also is recommended that epidemiological studies and clinical trials account for age, sex, and race in statistical models comparing urinary markers of kidney damage.

Microalbuminuria, originally described more than 3 decades ago as a predictor of nephropathy in patients who had type 1 diabetes mellitus and associated with higher cardiovascular risk, is now linked with increased risk for cardiovascular events rather than progression to end-stage kidney disease. This article reviews the role of microalbuminuria in the context of atherosclerotic vascular disease. It presents the methods for microalbuminuria assessment in clinical practice, its relations with other cardiovascular risk factors, and the pathophysiologic associations between microalbuminuria and vascular damage. In addition, this article discusses the prognostic significance of microalbuminuria for cardiovascular disease as well as existing therapeutic interventions for reducing urine albumin excretion in patients who are at high cardiovascular risk.

Microalbuminuria and peripheral artery disease represent 2 different forms of target organ damage due to raised blood pressure. The aim of this study was to investigate the association between blood pressure with microalbuminuria and the appearance of peripheral artery disease after more than a decade, and moreover, to address whether any relationship exists between microalbuminuria and peripheral disease in a Greek Caucasian population. In 1990, 635 normal subjects were examined and their blood pressure was recorded. Nine and 12 years later, subjects were reexamined and 361 of them (57%) were available at last visit for the determination of microalbuminuria and ankle-arm index. Microalbuminuria was detected in 35/361 (9.7%) and peripheral artery disease in 89/361 (24.7%). Both conditions were statistically correlated with pulse and systolic blood pressure at all time points during the 12-year follow-up period, while the relationship with diastolic and mean arterial pressure existed only for baseline values and was then abolished. Microalbuminuria was statistically correlated to peripheral artery disease (r = -0.460, p = 0.0001). Blood pressure levels seemed to predict the appearance of microalbuminuria and peripheral disease after 12 years. Microvasculature and macrovasculature abnormalities (microalbuminuria and peripheral disease, respectively) showed a significant relationship, suggesting a common pathogenetic mechanism.

One-third of normoalbuminuric type 1 diabetic patients show immunoreactive nephrin in urine. Offspring of type 2 diabetic patients are insulin-resistant and susceptible to the development of diabetes. We investigated whether the offspring of type 2 diabetic patients show nephrin in urine and whether possible nephrinuria is associated with insulin resistance.

Urinary proteins from timed overnight urine collections from 128 offspring of type 2 diabetic patients and 9 control subjects were analysed by western blotting using an antibody against nephrin. Glucose metabolism was assessed by OGTT and IVGTT and the euglycaemic-hyperinsulinaemic clamp technique.

Of the offspring, 12.5% were strongly and 14.1% weakly positive for a 100-kDa urinary protein. All controls were negative. During the first 10 min of an IVGTT, the offspring strongly positive for the urinary protein had a higher insulin response than the offspring without the protein (3,700 vs 2,306 pmol l(-1)min(-1), p=0.007). Insulin sensitivity (the rate of whole-body glucose uptake divided by the steady-state insulin level x 100) was lower among the offspring strongly positive for the urinary protein than among the offspring negative for the protein (11.3 vs 15.8 micromol kg(-1)min(-1)pmol(-1)l(-1), p=0.008).

A 100-kDa urinary protein detectable with a nephrin antibody is associated with insulin resistance in offspring of type 2 diabetic patients.

Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended to primary prevention for those subjects in the general population who are at risk for progressive renal failure, but who had never suffered from a primary renal disease. We show that such subjects can be detected by screening for albuminuria. Elevated urinary albumin loss is an indicator not only of poor renal, but also of poor cardiovascular prognosis. In addition to diabetic subjects who are at risk for albuminuria, we also show that hypertensive, obese, and smoking subjects are more susceptible. We suggest that therapies that have been shown to lower albumin excretion, such as ACE inhibitors, angiotensin II receptor antagonists, and statins be started early in such patients to prevent them from developing clinical renal disease and its attendant cardiovascular complications.

The purpose of this study was to examine sensory function and albumin excretion according to categories of glucose tolerance in individuals undergoing screening for diabetes.

Sensory function and albumin excretion measurements were obtained in 636 individuals at the time of screening for diabetes according to American Diabetes Association glucose tolerance criteria. Sensory thresholds were measured by forced-choice techniques. Albumin-to-creatinine ratios were calculated from spot urine samples.

Of 90 individuals whose glucose levels were in the range for diabetes, 65 had fasting glucose values >or=126 mg/dl, whereas 25 had 2-h glucose values >or=200 mg/dl, with fasting glucose values <126 mg/dl. In covariance analyses, those with fasting glucose levels >or=126 mg/dl had higher vibration (P < 0.01) and thermal (P < 0.05 for cool and warm) thresholds than those with normal glucose tolerance. This pattern was also evident for albumin-to-creatinine ratios (P < 0.001). In contrast, those with 2-h glucose values >or=200 mg/dl and fasting glucose values <126 mg/dl had sensory threshold and albumin-to-creatinine ratio values similar to those of the normal group. Individuals with fasting glucose levels >or=126 mg/dl had higher vibration threshold and albumin-to-creatinine ratio values (<0.05 and <0.01, respectively) than those with levels <126 mg/dl.

Sensory threshold and albumin excretion values already tend to be greater than normal at screening in individuals with fasting glucose levels >or=126 mg/dl, but not in those with levels <126 mg/dl. A reliance on fasting glucose levels >or=126 mg/dl for screening might not be sufficient for early intervention and the optimal prevention of diabetes complications.

Impaired glucose tolerance (IGT) serves as a marker for the state of insulin resistance and predicts both large- and small-vessel vascular complications, independent of a patient's progression to diabetes. Patients with IGT are at significantly increased risk for death and morbidity due to myocardial infarction, stroke, and large-vessel occlusive disease. IGT is more predictive of cardiovascular morbidity than impaired fasting glucose, probably because it is a better surrogate for the state of insulin resistance. IGT is also independently associated with traditional microvascular complications of diabetes, including retinopathy, renal disease, and polyneuropathy, which are the topics of this review. Inhibition of nitric oxide-mediated vasodilation, endothelial injury due to increased release of free fatty acids and adipocytokines from adipocytes, and direct metabolic injury of endothelial and end-organ cells contribute to vascular complications. Early detection of IGT allows intensive diet and exercise modification, which has proven significantly more effective than drug therapy in normalizing postprandial glucose and inhibiting progression to diabetes. To what degree intervention will limit recognized complications is not known.

Cardiovascular morbidity and mortality is not equally distributed among genders, men being more affected than women. It is not clear whether this is only related to a higher prevalence of the cardiovascular risk factors or to a similar prevalence of the risk factors as in women but a greater vascular susceptibility to these risk factors in men. This was tested by studying the association between various cardiovascular risk factors and urinary albumin excretion (UAE) in a large cohort of male and female subjects. While the prevalence of smoking and hypercholesterolemia was comparable between the genders, obesity was more common in women, and diabetes and hypertension were more frequent in men. The prevalence of microalbuminuria was about twofold higher in men. Interestingly, for a given level of any risk factor, UAE was higher in men than in women. On multivariate analysis with UAE as the dependent variable, an interaction with gender was found for the risk factors age, body mass index, and plasma glucose. Thus, for a higher age, body mass index, and glucose, the UAE is significantly increased in men when compared with women. It is concluded that gender differences exist in the association between cardiovascular risk factors and UAE. This is consistent with a larger vascular susceptibility to these risk factors in men as compared with women.

We aimed to compare levels of urinary albumin excretion and the prevalence of microalbuminuria in UK South Asians and Europeans. Microalbuminuria predicts cardiovascular disease in European origin populations, but evidence from the general population of South Asians is lacking. Coronary heart disease (CHD) mortality is 40-50% higher in UK South Asians compared with the whole population, for reasons that are incompletely understood.

Microalbuminuria was measured using the albumin-creatinine ratio in an age- and sex-stratified random sample of 1509 adults from European (n = 825), Indian (n = 259), Pakistani (n = 305) and Bangladeshi (n = 120) ethnic groups.

Levels of urinary albumin excretion were substantially higher in South Asians (geometric mean albumin creatinine ratio (95% confidence interval) 0.83 (0.75, 0.91)) than in Europeans (0.55 (0.51, 0.60)). Microalbuminuria was associated with older age, hypertension and diabetes, but independently of these risk factors urinary albumin excretion was higher in South Asians than Europeans.

Urinary albumin excretion is higher and microalbuminuria more frequent in UK South Asians compared with the majority ethnic population. Microalbuminuria may be relevant to the causal pathways leading to the excess of cardiovascular mortality and possibly renal failure in UK South Asians.

Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality. The effects of 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor (statin) therapy on proteinuria in normolipidemic patients with well-controlled hypertension have not been studied. A total of 63 normolipidemic (total cholesterol <240 mg/dL) and proteinuric (300 to 3000 mg/d) patients with well-controlled blood pressure (<140/90 mm Hg) were randomized to receive either placebo (n=32) or pravastatin (10 mg/d; n=31) after a 3-month placebo period. Pravastatin lowered proteinuria after 6 months by 54% (P<0.0001). Creatinine clearance was stable throughout the study in the 2 groups. Despite unchanged plasma endothelin-1 levels throughout the study, urinary excretion of the peptide was decreased and significantly correlated with improvement in urinary protein excretion in pravastatin-treated patients (r=0.64, P=0.001). The urinary excretion of retinol-binding protein decreased after pravastatin administration, probably reflecting an improvement in tubular function. In contrast, the urinary excretion of IgG did not change significantly throughout the study in either group. Multivariate analysis revealed that proteinuria was only significantly correlated with statin use (P<0.0001, R2= 0.66). Linear regression analysis in the statin-treated group did not show any correlation between changes in lipid profiles and proteinuria regression. Thus, in addition to their primary function of antilipidemia, the addition of pravastatin to treatment for well-controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and lipid-lowering effects, possibly through inhibiting renal endothelin-1 synthesis and improving tubular function.

To assess current and long-term associations of glycemia with microalbuminuria, a marker of generalized endothelial injury.

We measured clinical characteristics, fasting plasma glucose, and the urinary albumin-to-creatinine ratio (UACR) in 1,311 men and 1,518 women attending the sixth examination cycle (1995-1998) of the Framingham Offspring Study. After excluding participants with diabetes or cardiovascular disease (CVD) at the baseline examination (1971-1974), we used fasting glucose measured at baseline, examination 6, and at least two additional examinations from 1974 to 1995 in regression models to predict risk for microalbuminuria (UACR > or = 30 mg/g) associated with baseline, current, and 24-year time-integrated glycemia.

Microalbuminuria was present in 9.5% of men and 13.4% of women. Among men, age-adjusted odds ratios (95% CI) for microalbuminuria associated with each 0.28 mmol/l (5 mg/dl) increase in baseline, current, and time-integrated glucose levels were 1.12 (1.00-1.16), 1.08 (1.05-1.10), and 1.16 (1.11-1.21), respectively. These effects persisted after adjustment for systolic blood pressure and other confounders. Higher glucose levels also predicted incident diabetes and CVD. Mean time-integrated glucose levels were highest among men who developed both CVD and microalbuminuria (SE 6.82 +/- 0.16 mmol/l), intermediate among men with either condition (6.03 +/- 0.65 mmol/l), and lowest among men with neither condition (5.49 +/- 0.02 mmol/l; P < 0.001 for all pairwise comparisons). We observed similar associations in women.

Long-term hyperglycemia and subdiabetic glycemia increase risk for microalbuminuria. Microalbuminuria, type 2 diabetes, and CVD seem to arise together over the course of decades, consistent with the hypothesis that they share a common antecedent.

Microalbuminuria (MA) is associated with adverse health outcomes in diabetic and hypertensive adults. The prevalence and clinical significance of MA in nondiabetic populations is less clear. The purpose of this study was to generate national estimates of the prevalence of MA in the US population. Untimed urinary albumin concentrations (UACs) and creatinine concentrations were evaluated in a nationally representative sample of 22,244 participants aged 6 years and older. Persons with hematuria and menstruating or pregnant women were excluded from analysis. The percent prevalence of clinical proteinuria (UAC > or = 300 mg/L) was similar for males and females. However, the prevalence of MA (urinary albumin-creatinine ratio [ACR], 30 to 299 mg/g) was significantly lower in males (6.1%) compared with females (9.7%). MA prevalence was greater in children than young adults and increased continuously starting at 40 years of age. MA prevalence was greater in non-Hispanic blacks and Mexican Americans aged 40 to 79 years compared with similar-aged non-Hispanic whites. MA prevalence was 28.8% in persons with previously diagnosed diabetes, 16.0% in those with hypertension, and 5.1% in those without diabetes, hypertension, cardiovascular disease, or elevated serum creatinine levels. In adults aged 40+ years, after excluding persons with clinical proteinuria, albuminuria (defined as ACR > or = 30 mg/g) was independently associated with older age, non-Hispanic black and Mexican American ethnicity, diabetes, hypertension, and elevated serum creatinine concentration. MA is common, even among persons without diabetes or hypertension. Age, sex, race/ethnicity, and concomitant disease contribute to the variability of MA prevalence estimates.

This paper reviews the existing epidemiological and clinical evidence about the relationships of non-diabetic microalbuminuria with cardiovascular risk factors such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy, adverse metabolic status, smoking habits, elevated angiotensin II levels, endothelial dysfunction, acute and perhaps subclinical inflammation. Because of that unique property of reflecting the influence of so many clinically relevant parameters, microalbuminuria may legitimately be defined as an integrated marker of cardiovascular risk, an unique profile among the several prognostic predictors available to stratify risk in hypertensive patients. Recent cohort studies also showed associations with cardiovascular morbidity and mortality independently from conventional atherogenic factors. This behaviour, whose understanding still needs further elucidation, suggests to measure albuminuria and to screen patients at a higher absolute risk in whom preventive treatment is expected to be more beneficial than in those with a lower absolute risk.

Familial clustering of diabetes and nephropathy suggests that either common environmental or inherited mechanisms are important in developing diabetic nephropathy. If an inherited mechanism is important, the albumin excretion rate might be increased in those at future risk. This study aimed to determine whether people with a family history of diabetes or people with a family history of renal disease were most at risk.

In a two-by-two factorial study of urinary albumin in non-diabetic Polynesians, 90 people with a first degree relative (FDR) with end-stage renal failure (ESRF) and diabetes (group 1) were compared with 90 people with a FDR with non-diabetic ESRF (group 2), with 90 people with a FDR with diabetes but no known nephropathy (group 3) and 90 people with no known relatives with either diabetes or nephropathy (group 4). Groups were matched for ethnicity and age.

Subjects with a family history of ESRF (groups 1 and 2) had an increased mean albumin-creatinine ratio (1.25 vs. 1.00 mg/mmol, P = 0.01), but in subjects with a family history of diabetes (groups 1 and 3), the mean ratios were not significantly different from those without a family history of diabetes (1.06 vs. 1.17 mg/mmol; P = 0.2). In those with a family history of nephropathy, fasting blood glucose and systolic blood pressure were increased, while fasting insulin and 2 h insulin concentrations were lower. A family history of diabetes was associated with an increased fasting blood glucose and 2-h blood glucose. By multiple linear regression, the mean systolic blood pressure (P = 0.02), the 2-h glucose concentration (P = 0.05), a family history of renal failure (P = 0.04), female sex (P = 0.0001) and the total cholesterol (P = 0.01) were each independently associated with microalbuminuria, while a family history of diabetes was not (P = 0.09).

These data suggest that among Polynesians there is no specific inherited tendency to diabetic nephropathy per se. The risk of nephropathy does not appear to be associated with the degree of familial risk of diabetes itself. Rather, the risk of diabetic nephropathy may be the result of a familial risk of nephropathy from any cause and is associated with diabetes through relative hypoinsulinaemia and hyperglycaemia.

Microalbuminuria is associated with both an increased prevalence of cardiovascular risk factors and greater renal and cardiovascular morbidity. We questioned whether in the general population such associations can be found at lower levels of urinary albumin excretion than that of classically defined microalbuminuria. To that purpose urinary albumin concentration was measured in 40619 subjects aged 28 to 75 years. The subjects filled in a questionnaire on cardiovascular risk factors and events and were divided in deciles according to their urinary albumin concentration. Smoking was associated with albuminuria in the fifth or higher decile of urinary albumin concentration, that is with an albumin concentration of 5.1 mg/l and higher. The lower cut-off point for a positive association with hypertension was 8.8 mg/l, and for diabetes 11.2 mg/l. Family history for cardiovascular disease and hyperlipidaemia were not associated with albuminuria. We conclude that urinary albumin concentrations far below the microalbuminuric range are associated with increased prevalence of established cardiovascular risk factors. Family history for cardiovascular disease and hyperlipidaemia seems to behave differently. These data emphasize the need for more studies on the impact of albuminuria on the prediction of cardiovascular and renal disease in the general population.

While the ethnic make up of the New Zealand population is predominantly European, the Polynesian population, consisting of indigenous New Zealand Maori and more recent immigrants from the other Pacific Islands is increasing rapidly. The prevalence of diabetes in these Polynesians is high. There is also an increasing prevalence of obesity, and obesity is a greater problem amongst Polynesian people. The number of elderly people in the population is increasing. All of these demographic changes are increasing the incidence and prevalence of Type 2 diabetes. The incidence of Type 1 diabetes is also rising, although the reasons for this are unknown. Diabetic nephropathy is the most common cause of end stage renal failure in New Zealand. Polynesian people with diabetes, and in particular Maori, have a very high rate of diabetic nephropathy and develop renal failure at a more rapid rate than European patients with nephropathy relating to Type 1 diabetes. The propensity for Maori patients with Type 2 diabetes to develop renal failure may relate to a younger age at the onset of diabetes, a genetic susceptibility to nephropathy, and socio-economic or cultural factors leading to less adequate medical care.

In non-insulin-dependent diabetes mellitus (NIDDM), there is a clustering of an elevated urinary albumin excretion rate (U-AER) in nondiabetic relatives of albuminuric patients. Whether this is also the case in insulin-dependent diabetes mellitus (IDDM) is unknown.

Overnight U-AER was measured in 186 nondiabetic first-degree relatives of 80 IDDM patients with diabetic nephropathy (U-AER > 200 microg/min or 300 mg/24 hours; DN+) and in 52 relatives of 25 IDDM patients without nephropathy (U-AER < 20 microg/min; DN-). The two groups of relatives were comparable regarding gender distribution, age, obesity, blood pressure, prevalence of antihypertensive therapy, and smoking habits.

No difference was found in overnight U-AER between relatives of patients with DN+ and DN- [median (range), 3.4 (0.1 to 372) vs. 4.0 (0.2 to 62) microg/min, respectively, P = NS]. The proportion of relatives with a U-AER = 10 microg/min was 12% in DN+ compared with 8% in DN- (P = NS). Among relatives of DN+, those with antihypertensive treatment (AHT+) had higher U-AER compared with those without [AHT+ vs. AHT-, 5.0 (0.5 to 372) vs. 3.4 (0.1 to 26.5) microg/min, P < 0.01], a phenomenon that was not seen among relatives of DN-[AHT + vs. AHT-, 3.6 (2.1 to 24.3) vs. 4.0 (0. 2 to 61.5) microg/min, P = NS]. However, this analysis was impaired by the small number of relatives of DN- with hypertension (N = 7).

In IDDM, we found no clustering of elevated U-AER in nondiabetic relatives of patients with nephropathy. This is different from what has been reported in NIDDM, and suggests heterogeneity in the genesis of albuminuria in diabetes.

Some patients with essential hypertension manifest greater than normal urinary albumin excretion (UAE). The significance of this association, which is the object of this review, is not well established. Hypertensive patients with microalbuminuria manifest greater levels of blood pressure, particularly at night, and higher serum levels of cholesterol, triglycerides, and uric acid than patients with normal UAE. Levels of high-density lipoprotein cholesterol, on the other hand, were lower in patients with microalbuminuria than in those with normal UAE. Patients with microalbuminuria manifested greater incidence of insulin resistance and thicker carotid arteries than patients with normal UAE. After a follow-up of 7 years, we observed that 12 cardiovascular events occurred among 54 (21.3%) patients with microalbuminuria and only two such events among 87 patients with normal UAE (P < 0.0002). Stepwise logistic regression analysis showed that UAE, cholesterol level, and diastolic blood pressure were independent predictors of the cardiovascular outcome. Rate of creatinine clearance from patients with microalbuminuria decreased more than that from those with normal UAE. In conclusion, these studies suggest that hypertensive individuals with microalbuminuria manifest a variety of biochemical and hormonal derangements with pathogenic potential, which results in hypertensive patients having a greater incidence of cardiovascular events and a greater decline in renal function than patients with normal UAE.

Microalbuminuria in non-diabetic subjects is reportedly associated with increased cardiovascular morbidity and mortality. The prevalence of microalbuminuria in non-diabetic subjects varies widely from 5-6% in the UK and USA to 30-55% in Finland, Mexico, or Australian Aborigines. We studied cross-sectionally 497 clinically healthy, non-diabetic subjects more than 40 years of age who were living in Seoul, Korea for the prevalence of microalbuminuria and various cardiovascular risk factors. Urinary albumin-to-creatinine ratio (UACR) was determined in morning spot urine samples. Subjects were divided into normoalbuminuria (UACR < 2 mg/mmol) and microalbuminuria (UACR > or = 2 mg/mmol) groups. A total of 61 (12.2%) out of 497 subjects were found to have microalbuminuria. Subjects with microalbuminuria had significantly higher values in age, body mass index (BMI), waist-to-hip ratio in women, systolic and diastolic blood pressure, prevalence of hypertension, plasma cholesterol and triglyceride, and fasting plasma insulin. When subjects with microalbuminuria were compared with age-, sex-, and BMI-matched controls without microalbuminuria, systolic and diastolic blood pressure, and fasting plasma insulin concentrations were higher in microalbuminuric subjects. Multiple logistic regression analysis showed that fasting plasma insulin level and systolic blood pressure were independently associated with microalbuminuria. These results indicate that the prevalence of microalbuminuria in Korean non-diabetic subjects is lower than that in Mexico and Finland, but similar to that in Caucasians from the UK and USA, or in Pima Indians. Also, microalbuminuria in Korean non-diabetic subjects is associated with atherosclerotic risk factors such as hyperinsulinemia and hypertension, suggesting that microalbuminuria in these subjects may be a feature of insulin resistance syndrome.

There is little published data on the incidence of remote hypertension, microalbuminuria (a possible marker of remote cardiovascular events) and diabetes following preeclampsia. This is of particular importance in Pacific Island populations as they have a high rate of preeclampsia, non-insulin dependent diabetes and cardiovascular related deaths. The aim of this study was to compare the rate of microalbuminuria and hypertension in 50 Samoan women with past preeclampsia (cases) with 50 Samoan women who did not have past preeclampsia (controls). Forty per cent of cases were hypertensive at follow-up compared to 2% in the control group (p < 0.0001). Microalbuminuria or proteinuria occurred in 40% of women with past preeclampsia and 18% of controls (p < 0.02). Half of the cases with microalbuminuria were hypertensive. No case or control had an elevated fructosamine, suggesting that current diabetes was an unlikely explanation for the microalbuminuria. We conclude that Samoan women with past preeclampsia are at increased risk of developing chronic hypertension and microalbuminuria. The significance of the microalbuminuria after preeclampsia is not known, but it may be a marker of either remote cardiovascular morbidity or non-insulin dependent diabetes. This study raises longterm health implications for women with preeclampsia.

Polynesian (59 Maori and 30 Pacific Island) patients were identified from two diabetes clinic registers and followed for a mean of 4.8 years, in order to determine the prognostic significance of urinary albumin excretion. Events were defined as death or entry onto a renal replacement programme. Fourteen events occurred during the period of follow-up. Urinary albumin/creatinine ratio was treated as a continuous variable in a proportional hazards analysis. A 10-fold increase in albumin/creatinine ratio was associated with a 5-fold increase in the risk of an event (95% C.I. = 2.05-12.09). In conclusion, elevated urinary albumin/creatinine predicted mortality and renal morbidity in Maori and Pacific Island patients with non-insulin-dependent diabetes.

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.

Microalbuminuria in the general population is associated with recognized risk factors for cardiovascular disease such as hypertension, hyperglycemia, hyperinsulinemia, and hyperlipidemia; and it is an independent predictor of subsequent cardiovascular mortality in hypertensive, diabetic, and elderly populations. Although different methods have been used for measuring and expressing urinary albumin excretion and a variety of cutoff levels have been used for defining microalbuminuria, prevalence of microalbuminuria appears to be higher in non-Europeans (8%-28%) than in Europeans (2%-10%). However, because of the large within-individual variability of urinary albumin excretion and the relatively low prevalence of microalbuminuria, large studies are required to detect statistically significant associations between albuminuria and cardiovascular risk factors. Evidence presented here supports the proposition that microalbuminuria represents a marker of cardiovascular disease risk in nondiabetic individuals as well as diabetic individuals. Moreover, because of a high sensitivity of the test and because albuminuria is a concomitant of many forms of renal disease, microalbuminuria also has a role in detecting patients with renal involvement associated with essential hypertension, lupus erythematosus, women with pre-eclampsia, and subjects with unsuspected primary and secondary nephropathies.