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Biomedical subjects

Robert G Nelson

Publications and source records attributed to Robert G Nelson.

At least 19 recordsLinked to original sources
PubMed2007

Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes.

OBJECTIVE: To assess the role of homocysteine as a risk factor for mortality in diabetic subjects. METHODS: Homocysteine, vitamin B(12), and folate concentrations were measured in stored sera of 396 diabetic Pima Indians aged > or = 40 years when examined between 1982 and 1985. Vital status was assessed through 2001. RESULTS AND CONCLUSIONS: Over a median follow-up of 15.7 years, there were 221 deaths-76 were due to cardiovascular disease (CVD), 36 to diabetes/nephropathy and 34 to infections. Homocysteine was positively associated with mortality from all causes (hazard rate ratio (HRR) for highest versus lowest tertile of homocysteine = 1.70, 95% confidence interval (CI) 1.18-2.46), from diabetes/nephropathy (HRR = 2.39, 95% CI 0.94-6.11) and from infectious diseases (HRR = 3.39, 95% CI 1.19-9.70), but not from CVD (HRR = 1.16, 95% CI 0.62-2.17) after adjustment for age, sex and diabetes duration. Homocysteine correlated with serum creatinine (r = 0.50), and the relationships with mortality rates were not significant after adjustment for creatinine. Vitamin B(12) was positively associated with all-cause mortality (HRR for 100 pg/mL difference adjusted for age, sex and diabetes duration = 1.15, 95% CI 1.08-1.22) and death from diabetes/nephropathy (HRR = 1.27, 95% CI 1.10-1.46). The association between homocysteine and mortality in type 2 diabetes is not causal, but is confounded by renal disease in Pima Indians.

Adult↗
PubMed2006

The new KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and CKD.

BACKGROUND/AIMS: The National Kidney Foundation (NKF) recently published new guidelines and clinical practice recommendations for the diagnosis and management of patients with diabetes and chronic kidney disease (CKD). METHODS: Guidelines were developed using an evidence-based approach. When sufficient evidence was lacking, recommendations were developed that reflect expert opinion. RESULTS: Guidelines describe the process for screening and diagnosis of kidney disease in the setting of diabetes and the management of hyperglycemia, hypertension, dyslipidemia, and nutrition. Recommendations describe the management of albuminuria in the normotensive diabetic patient and the potential value of albuminuria as a marker of treatment efficacy; the impact of diabetes and CKD in special populations; the importance of behavioral self-management; and the value of intensive multifaceted intervention in these high risk patients. CONCLUSIONS: The new guidelines and recommendations update and extend the scope of the NKF's Kidney Disease Outcomes Quality Initiative (KDOQI(TM)).

Diabetes Complications↗
PubMed2006

Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians.

CONTEXT: The long-term outcome of persons with youth-onset type 2 diabetes mellitus has not been well described. OBJECTIVE: To compare incidence of diabetic end-stage renal disease (ESRD) and mortality in Pima Indians with youth- and older-onset type 2 diabetes mellitus. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal population-based study conducted between 1965 and 2002 in Pima Indians from the state of Arizona. Participants were divided into 2 groups: (1) youth-onset type 2 diabetes mellitus (onset <20 years of age) and (2) older-onset type 2 diabetes mellitus (onset > or =20 - <55 years of age). Events and person-years of follow-up were stratified in a time-dependent fashion by decades of age. End-stage renal disease was defined as dialysis attributed to diabetic nephropathy or death from diabetic nephropathy. MAIN OUTCOME MEASURES: Incidence rate of diabetic ESRD and mortality between 25 and 55 years of age, according to age at onset of type 2 diabetes mellitus. RESULTS: Among the 1856 diabetic participants, 96 had youth-onset type 2 diabetes mellitus. The age-sex-adjusted incidence of diabetic ESRD was 25.0 cases per 1000 person-years (95% confidence interval [CI], 6.7-43.1) in youth-onset diabetes mellitus and 5.4 cases per 1000 person-years (95% CI, 4.4-6.4) in older-onset diabetes mellitus (incidence rate ratio, 4.6; 95% CI, 2.2-9.8). Age-specific incidence rates were higher in participants with youth-onset diabetes mellitus at all ages. Between 25 and 55 years of age, the age-sex-adjusted death rate from natural causes was 15.4 deaths per 1000 person-years (95% CI, 0.2-30.5) in participants with youth-onset diabetes mellitus and 7.3 deaths per 1000 person-years (95% CI, 5.9-8.7) in individuals with older-onset diabetes mellitus (death rate ratio, 2.1; 95% CI, 0.8-5.7). Compared with nondiabetic participants, the death rate was 3.0 times as high in individuals with youth-onset diabetes mellitus (95% CI, 1.1-8.0) and 1.4 times as high in individuals with older-onset diabetes mellitus (95% CI, 1.1-1.8). In a subset of 1386 participants with complete data for all covariates who were observed from the onset of diabetes mellitus, the age at onset of diabetes mellitus was not associated with the incidence of ESRD (hazard ratio, 1.0; 95% CI, 0.9-1.2) after adjusting for sex, mean arterial pressure, body mass index (calculated as weight in kilograms divided by height in meters squared), plasma glucose concentration, smoking, hypoglycemic medicines, and blood pressure medicines in a Cox proportional-hazards model. CONCLUSIONS: Early-onset type 2 diabetes mellitus is associated with substantially increased incidence of ESRD and mortality in middle age. The longer duration of diabetes mellitus by middle age in individuals diagnosed younger than age 20 years largely accounts for these outcomes.

Adolescent↗
PubMed2006

Electrocardiographic abnormalities predict deaths from cardiovascular disease and ischemic heart disease in Pima Indians with type 2 diabetes.

BACKGROUND: The association between electrocardiographic (ECG) abnormalities and deaths from cardiovascular diseases (CVD) and ischemic heart disease (IHD) has been reported in the general population, but there is little information regarding persons with type 2 diabetes. METHODS: Minor and major ECG abnormalities were identified and classified according to the Minnesota Code in a longitudinal study of 1605 Pima Indians aged > or =35 years with type 2 diabetes. Underlying causes of death were determined by review of all available clinical records, autopsy reports, medical examiners' findings, and death certificates. RESULTS: During a median follow-up of 14.1 years (range 0.1 to 33.8 years), there were 190 CVD deaths, 135 (71.1%) of which were attributable to IHD. The age-adjusted CVD death rates in men with none, minor, and major ischemic ECG abnormalities were 7.3, 12.2 and 27.8, and in women, 4.3, 4.8 and 12.5 per 1000 person-years, respectively. After adjustment for other co-variables in a multiple proportional hazards model, subjects with minor and major ischemic abnormalities on ECG had 1.22 (95% CI, 0.76-1.97) and 1.83 (95% CI, 1.21-2.76) times the CVD death rate, and 1.32 (95% CI, 0.70-2.50) and 2.12 (95% CI, 1.26-3.57) times the IHD death rate of those with no ischemic ECG abnormalities, respectively. CONCLUSIONS: The CVD and IHD death rates were higher in men and in subjects with major ischemic ECG abnormalities. Major ischemic abnormalities on ECG predicted death after accounting for other cardiovascular risk factors, including proteinuria.

Adult↗
PubMed2006

Kidney disease among the indigenous peoples of Oceania.

The prevalence of kidney disease is increasing among the indigenous peoples of Oceania--the region of the world that includes Australia, New Zealand, Papua New Guinea, and thousands of smaller islands. The number of indigenous people with early kidney disease is hard to quantify, but risk factors, including hypertension and diabetes, are widespread. The incidence of kidney failure is known in major population centers, where dialysis treatments are available, but few data are available elsewhere in Oceania. Nevertheless, the incidence of end-stage renal disease among Aborigines, Torres Straits Islanders, Pacific Islanders and Maori is considerably higher than in the surrounding non-indigenous populations, and most of the kidney failure is attributed to diabetes. Despite the high incidence of kidney failure among indigenous people, few receive kidney transplants, and geographic and economic constraints limit the availability of dialysis treatment. Consequently, clinical management should emphasize prevention, screening, and early intervention.

Adult↗
PubMed2005

Modeling GFR trajectories in diabetic nephropathy.

In an 8-year longitudinal study of Pima Indians with type 2 diabetes and nephropathy, we used statistical techniques that are novel and depend on minimal assumptions to compare longitudinal measurements of glomerular filtration rate (GFR). Individuals enrolled with new-onset microalbuminuria either progressed to macroalbuminuria (progressors, n = 13) or did not progress (nonprogressors, n = 13) during follow-up. Subjects with new-onset macroalbuminuria at screening were also followed (n = 22). Patients had their GFR determined serially by urinary iothalamate clearances (average 11 clearances; range 6-19). GFR courses of individuals were modeled using an adaptation of smoothing and regression cubic B-splines. Group comparisons were based on five-component vectors of fitted GFR values using a permutation approach to a Hotelling's T(2) statistic. GFR profiles of initially microalbuminuric progressors differed significantly from those of nonprogressors (P = 0.003). There were no significant baseline differences between progressors and nonprogressors with respect to any measured clinical parameters. The course of GFR in the first 4 yr following progression to macroalbuminuria in initially microalbuminuric subjects did not differ from that in newly screened macroalbuinuric subjects (P = 0.27). Without imposing simplifying models on the data, the statistical techniques used demonstrate that the courses of decline of GFR in definable subgroups of initially microalbuminuric diabetic Pima Indians, although generally progressive, follow distinct trajectories that are related to the extent of glomerular barrier dysfunction, as reflected by the evolution from microalbuminuria to macroalbuminuria.

Adult↗
PubMed2005

Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study.

Research on early renal function decline in diabetes is hampered by lack of simple tools for detecting trends (particularly systematic decreases) in renal function over time when GFR is normal or elevated. This study sought to assess how well serum cystatin C meets that need. Thirty participants with type 2 diabetes in the Diabetic Renal Disease Study met these three eligibility criteria: GFR >20 ml/min per 1.73 m2 at baseline (based on cold iothalamate clearance), 4 yr of follow-up, and yearly measurements of iothalamate clearance and serum cystatin C. With the use of linear regression, each individual's trend in renal function over time, expressed as annual percentage change in iothalamate clearance, was determined. Serum cystatin C in mg/L was transformed to its reciprocal (100/cystatin C), and linear regression was used to determine each individual's trend over time, expressed as annual percentage change. In paired comparisons of 100/cystatin C with iothalamate clearance at each examination, the two measures were numerically similar. More important, the trends in 100/cystatin C and iothalamate clearance were strongly correlated (Spearman r = 0.77). All 20 participants with negative trends in iothalamate clearance (declining renal function) also had negative trends for 100/cystatin C. Results were discordant for only three participants. In contrast, the trends for three commonly used creatinine-based estimates of GFR compared poorly with trends in iothalamate clearance (Spearman r < 0.35). Serial measures of serum cystatin C accurately detect trends in renal function in patients with normal or elevated GFR and provide means for studying early renal function decline in diabetes.

Adult↗
PubMed2005

Diabetic end-stage renal disease in the indigenous population of the Commonwealth of the Northern Mariana Islands.

The number of cases of treated end-stage renal disease (ESRD) attributable to type 2 diabetes and survival after the onset of renal replacement therapy was examined in the Commonwealth of the Northern Mariana Islands (CNMI). All Chamorros and Carolinians to receive renal replacement therapy for ESRD between January 1982 and December 2002 were identified. Changes in survival over time were examined by dividing the study into three equal periods. Of 180 new cases of ESRD, 137 (76%; 101 Chamorros, 36 Carolinians) were attributed to diabetes. Ninety-nine subjects, 80% of whom had diabetic ESRD, began renal replacement therapy in the last 7 years of the study compared with 81 (72% with diabetic ESRD) in the previous 14 years. All 137 of the diabetic subjects received haemodialysis. During the 21-year study period, 79 of the diabetic subjects receiving dialysis died. The median survival after the onset of haemodialysis was 37 months in the first time period (1982-1988), 47 months in the second period (1989-1995) and 67 months in the third period (1996-2002). The death rate in the first period was 4.3 times (95% CI, 2.1-8.9) as high and the second period was 2.9 times (95% CI, 1.5-5.8) as high as the most recent period, after adjustment for age, sex and ethnicity in a proportional-hazards analysis. The number of diabetic patients in CNMI who are receiving renal replacement therapy is rising rapidly. Considerable improvement in survival after the onset of haemodialysis has occurred over the past 21 years.

Adult↗
PubMed2005

Predominant effect of kidney disease on mortality in Pima Indians with or without type 2 diabetes.

BACKGROUND: We examined the effect of kidney disease (KD) on mortality in nondiabetic and diabetic Pima Indians aged > or = 45 years old. METHODS: Deaths and person-years of follow-up were stratified in a time-dependent fashion into categories of (1) no proteinuria and normal serum creatinine (SCr); (2) proteinuria and normal SCr; (3) high SCr [SCr > or = 133 micromol/L (1.5 mg/dL) in men, > or = 124 micromol/L (1.4 mg/dL) in women] but not on renal replacement therapy (RRT); or (4) RRT. RESULTS: Among 1993 subjects, 55.8% had type 2 diabetes at baseline. Overall death rates increased with declining kidney function in both the nondiabetic and diabetic subjects (P < 0.0001). Death rates were similar in nondiabetic and diabetic subjects with comparable levels of kidney function, although the number of deaths among nondiabetic subjects with advanced KD was small. Infections and malignancy were the leading causes of death in nondiabetic subjects with KD. Among diabetic subjects, overall mortality increased with diabetes duration (P = 0.0001) and was highest in those on RRT (P < 0.0001). High SCr was associated with higher death rates from cardiovascular disease (CVD), diabetic nephropathy (DN), infections, and malignancy. CONCLUSION: Death rates increased comparably with worsening kidney function in both nondiabetic and diabetic subjects and were similar in nondiabetic and diabetic subjects without KD. KD was associated with excess mortality from DN, CVD, infections, and malignancy in diabetic subjects, and from infections in those without diabetes.

Adult↗
PubMed2005

Impact of lifestyle on prevalence of kidney disease in Pima Indians in Mexico and the United States.

Pima Indians in the United States and Mexico share a common genetic background but have very different lifestyles. Comparisons were made of the frequency of obesity, diabetes, hypertension, and kidney disease in these geographically separated but susceptible populations. Mexican Pimas had higher levels of physical activity, less obesity, and a lower prevalence of diabetes than their US Pima counterparts. Mean blood pressure rose with worsening glucose tolerance, and the prevalence of elevated urinary albumin excretion was higher in patients with diabetes than in those without, regardless of whether they lived in the United States or Mexico. These findings illustrate the importance of lifestyle in the development of diabetes and in the subsequent occurrence of diabetic kidney disease.

Adult↗
PubMed2005

Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress.

Dicarbonyl and oxidative stress may play important roles in the development of diabetes complications, and their response to hyperglycemia could determine individual susceptibility to diabetic nephropathy. This study examines the relationship of methylglyoxal, 3-deoxyglucosone (3DG), and oxidative stress levels to diabetic nephropathy risk in three populations with diabetes. All subjects in the Overt Nephropathy Progressor/Nonprogressor (ONPN) cohort (n = 14), the Natural History of Diabetic Nephropathy study (NHS) cohort (n = 110), and the Pima Indian cohort (n = 45) were evaluated for clinical nephropathy, while renal structural measures of fractional mesangial volume [Vv(Mes/glom)] and glomerular basement membrane (GBM) width were determined by electron microscopy morphometry in the NHS and Pima Indian cohorts. Methylglyoxal and 3DG levels reflected dicarbonyl stress, while reduced glutathione (GSH) and urine 8-isoprostane (8-IP) measured oxidative stress. Cross-sectional measures of methylglyoxal production by red blood cells incubated in 30 mmol/l glucose were increased in nephropathy progressors relative to nonprogressors in the ONPN (P = 0.027) and also reflected 5-year GBM thickening in the NHS cohort (P = 0.04). As nephropathy progressed in the NHS cohort, in vivo levels of methylglyoxal (P = 0.036), 3DG (P = 0.004), and oxidative stress (8-IP, P = 0.007 and GSH, P = 0.005) were seen, while increased methylglyoxal levels occurred as nephropathy progressed (P = 0.0016) in the type 2 Pima Indian cohort. Decreased glyceraldehyde-3-phosphate dehydrogenase activity also correlated with increased methylglyoxal levels (P = 0.003) in the NHS cohort. In conclusion, progression of diabetic nephropathy is significantly related to elevated dicarbonyl stress and possibly related to oxidative stress in three separate populations, suggesting that these factors play a role in determining individual susceptibility.

Adolescent↗
PubMed2005

Periodontal disease and mortality in type 2 diabetes.

OBJECTIVE: Periodontal disease may contribute to the increased mortality associated with diabetes. RESEARCH DESIGN AND METHODS: In a prospective longitudinal study of 628 subjects aged > or =35 years, we examined the effect of periodontal disease on overall and cardiovascular disease mortality in Pima Indians with type 2 diabetes. Periodontal abnormality was classified as no or mild, moderate, and severe, based on panoramic radiographs and clinical dental examinations. RESULTS: During a median follow-up of 11 years (range 0.3-16), 204 subjects died. The age- and sex-adjusted death rates for all natural causes expressed as the number of deaths per 1,000 person-years of follow-up were 3.7 (95% CI 0.7-6.6) for no or mild periodontal disease, 19.6 (10.7-28.5) for moderate periodontal disease, and 28.4 (22.3-34.6) for severe periodontal disease. Periodontal disease predicted deaths from ischemic heart disease (IHD) (P trend = 0.04) and diabetic nephropathy (P trend < 0.01). Death rates from other causes were not associated with periodontal disease. After adjustment for age, sex, duration of diabetes, HbA1c, macroalbuminuria, BMI, serum cholesterol concentration, hypertension, electrocardiographic abnormalities, and current smoking in a proportional hazards model, subjects with severe periodontal disease had 3.2 times the risk (95% CI 1.1-9.3) of cardiorenal mortality (IHD and diabetic nephropathy combined) compared with the reference group (no or mild periodontal disease and moderate periodontal disease combined). CONCLUSIONS: Periodontal disease is a strong predictor of mortality from IHD and diabetic nephropathy in Pima Indians with type 2 diabetes. The effect of periodontal disease is in addition to the effects of traditional risk factors for these diseases.

Adolescent↗
PubMed2004

Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes.

Adiponectin is produced exclusively by adipocytes, and its serum concentration is inversely associated with adiposity. This study examines the relationship among diabetes, renal function, and serum adiponectin in Pima Indians. Serum adiponectin was measured in 1069 people in whom glycemia and renal function had been measured. Serum adiponectin, adjusted for age, sex, and body mass index, was lowest in those with impaired glucose regulation or diabetes of less than 10 yr duration and highest in those with normal glucose tolerance or diabetes of duration of at least 10 yr. Both urinary albumin to creatinine ratio (ACR) and serum creatinine were positively correlated with adiponectin (Spearman's r = 0.43; P < 0.0001, and r = 0.37; P < 0.0001, respectively) in diabetic subjects. After stratification by albuminuria (normoalbuminuria ACR < 30 mg/g, microalbuminuria ACR = 30-299 mg/g, and macroalbuminuria ACR >or= 300 mg/g), the highest adiponectin concentration was in the macroalbuminuria group (geometric mean = 9.6 microg/ml) and the lowest was in the normoalbuminuric group (geometric mean = 5.6 microg/ml). After adjustment for age, sex, body mass index, and diabetes duration, the serum adiponectin concentration in the macroalbuminuria group was significantly higher than in both other groups (P < 0.0001). Serum adiponectin is lowest in the presence of impaired glucose regulation and early diabetes. In the presence of diabetes, serum adiponectin is positively associated with abnormal renal function and diabetes duration.

Adiponectin↗
PubMed2004

An explanation for the increase in heart disease mortality rates in diabetic Pima Indians: effect of renal replacement therapy.

OBJECTIVE: Diabetic nephropathy (DN) became the leading cause of death in diabetic Pima Indians in the 1970s, but was superseded by ischemic heart disease (IHD) in the 1980s. This study tests the hypothesis that the rise in the IHD death rate between 1965 and 1998 is attributable to access to renal replacement therapy (RRT). RESEARCH DESIGN AND METHODS: Underlying causes of death were determined among 2,095 diabetic Pima Indians > or = 35 years old during four 8.5-year time intervals. To assess the effect of access to RRT on IHD death rates, trends were reexamined after subjects receiving RRT were classified as if they had died of DN. RESULTS: During a median follow-up of 11.1 years (range 0.01-34), 818 subjects died. The age- and sex-adjusted DN death rate decreased over the 34-year study (P = 0.05), whereas the IHD death rate increased from 3.3 deaths/1,000 person-years (95% CI 1.4-5.2) to 6.3 deaths/1,000 person-years (95% CI 4.5-8.0; P = 0.03). After 151 subjects on RRT were reclassified as if they had died of DN, the death rate for DN increased from 4.8 deaths/1,000 person-years (95% CI 2.6-7) to 11.3 deaths/1,000 person-years (95% CI 9-13.6; P = 0.0007), whereas the increase in the IHD death rate disappeared (P = 0.57). CONCLUSIONS: The incidence rate of renal failure attributable to diabetes has increased rapidly over the past 34 years in Pima Indians. IHD has emerged as the leading cause of death due largely to the availability of RRT and to changes in the pattern of death among those with DN.

Age Distribution↗
PubMed2003

Testing for microalbuminuria in 2002: barriers to implementing current guidelines.

BACKGROUND: Testing for microalbuminuria is recommended to detect early kidney damage in patients with diabetes or other diseases. However, few studies have examined laboratory practices for microalbuminuria testing in the general community. METHODS: In 2002, all laboratories in Montana and reference laboratories used by Montana laboratories for microalbuminuria measurement were surveyed by mail to ascertain if they provided testing for microalbuminuria, specific tests performed, and units and cutoff values used to report microalbuminuria results. RESULTS: One hundred three of 126 laboratories (82%) responded to the survey. Overall, 79% of laboratories offered quantitative testing for microalbuminuria, either on site or through a reference laboratory. Twenty-five laboratories (24%) surveyed provided quantitative testing for microalbuminuria on site. Only 14 of 23 laboratories offering albumin-creatinine ratios on site reported results in units and cutoff values consistent with current recommendations. Fewer laboratories provided 24-hour (6 of 17 laboratories) or other timed (2 of 7 laboratories) testing, and many of these laboratories did not report results using recommended units and cutoff values. Overall, only 11 of 25 laboratories (44%) with on-site testing reported microalbuminuria values from 1 or more types of specimens exclusively using recommended units and cutoff values. CONCLUSION: Quantitative testing for microalbuminuria is not offered universally, and results often are reported in units and cutoff values that differ from current clinical recommendations.

Albuminuria↗
PubMed2003

Intrauterine determinants of diabetic kidney disease in disadvantaged populations.

Disadvantaged populations worldwide are experiencing an increasing incidence of kidney disease, much of which is attributable to diabetes. This report reviews the evidence that intrauterine exposure to growth retardation, diabetes, and vitamin A deficiency contribute disproportionately to the rising incidence of kidney disease in disadvantaged people, because they encounter these exposures more frequently than people from developed countries. These abnormal intrauterine exposures reduce nephron mass by impairing nephrogenesis, thereby increasing the susceptibility to kidney damage from diseases such as hypertension and diabetes that commonly affect disadvantaged people.

Diabetic Nephropathies↗