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Gregory A. Nichols

Bio: Gregory A. Nichols is an academic researcher from Kaiser Permanente. The author has contributed to research in topics: Type 2 diabetes & Diabetes mellitus. The author has an hindex of 18, co-authored 19 publications receiving 5997 citations.

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Journal ArticleDOI
TL;DR: The data suggest that efforts to reduce mortality in this population should be focused on treatment and prevention of coronary artery disease, congestive heart failure, diabetes mellitus, and anemia.
Abstract: Background Chronic kidney disease is the primary cause of end-stage renal disease in the United States. The purpose of this study was to understand the natural history of chronic kidney disease with regard to progression to renal replacement therapy (transplant or dialysis) and death in a representative patient population. Methods In 1996 we identified 27 998 patients in our health plan who had estimated glomerular filtration rates of less than 90 mL/min per 1.73 m 2 on 2 separate measurements at least 90 days apart. We followed up patients from the index date of the first glomerular filtration rates of less than 90 mL/min per 1.73 m 2 until renal replacement therapy, death, disenrollment from the health plan, or June 30, 2001. We extracted from the computerized medical records the prevalence of the following comorbidities at the index date and end point: hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, hyperlipidemia, and renal anemia. Results Our data showed that the rate of renal replacement therapy over the 5-year observation period was 1.1%, 1.3%, and 19.9%, respectively, for the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) stages 2, 3, and 4, but that the mortality rate was 19.5%, 24.3%, and 45.7%. Thus, death was far more common than dialysis at all stages. In addition, congestive heart failure, coronary artery disease, diabetes, and anemia were more prevalent in the patients who died but hypertension prevalence was similar across all stages. Conclusion Our data suggest that efforts to reduce mortality in this population should be focused on treatment and prevention of coronary artery disease, congestive heart failure, diabetes mellitus, and anemia.

1,580 citations

Journal ArticleDOI
TL;DR: The very low expenditures per capita in poor countries indicate that more resources are required to provide basic diabetes care in such settings as well as indicating that more prevention efforts are needed to reduce this burden.

998 citations

Journal ArticleDOI
TL;DR: The multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity.
Abstract: OBJECTIVE —The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up. RESEARCH DESIGN AND METHODS —We performed a retrospective cohort study of 8,231 patients with type 2 diabetes and 8,845 nondiabetic patients of similar age and sex who did not have CHF as of 1 January 1997, following them for up to 72 months to estimate the CHF incidence rate. In the diabetic cohort, we constructed a Cox regression model to identify risk factors for CHF development. RESULTS —Patients with diabetes were much more likely to develop CHF than patients without diabetes (incidence rate 30.9 vs. 12.4 cases per 1,000 person-years, rate ratio 2.5, 95% CI 2.3–2.7). The difference in CHF development rates between persons with and without diabetes was much greater in younger age-groups. In addition to age and ischemic heart disease, poorer glycemic control (hazard ratio 1.32 per percentage point of HbA 1c ) and greater BMI (1.12 per 2.5 units of BMI) were important predictors of CHF development. CONCLUSIONS —The CHF incidence rate in type 2 diabetes may be much greater than previously believed. Our multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity. Younger patients may benefit most from risk factor modification.

705 citations

Journal ArticleDOI
TL;DR: In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF.
Abstract: OBJECTIVE —To estimate the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and to identify risk factors for diabetes-associated CHF. RESEARCH DESIGN AND METHODS —We searched the inpatient and outpatient electronic medical records of 9,591 individuals diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex-matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, we searched forward for 30 months for incident cases of CHF. We constructed multiple logistic regression models to identify risk factors for both prevalent and incident CHF. RESULTS —CHF was prevalent in 11.8% ( n = 1,131) of diabetic subjects and 4.5% ( n = 435) of control subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline, and improved glycemic and blood pressure control at follow-up predicted the development of CHF. CONCLUSIONS —Despite controlling for age, duration of diabetes, presence of ischemic heart disease, and presence of hypertension, insulin use was associated with both prevalent and incident CHF. Why insulin use and better glycemic control both at baseline and follow-up independently predicted CHF deserves further study.

549 citations

Journal ArticleDOI
TL;DR: Clinicians should change glucose-lowering treatments in type 2 diabetes much sooner or use treatments that are less likely to fail, as well as predict when HbA(1c) would continue to deteriorate.
Abstract: OBJECTIVE—In type 2 diabetes, therapies to maintain blood glucose control usually fail after several years. We estimated the glycemic burden that accumulates from treatment failure and describe the time course and predictors of failure. RESEARCH DESIGN AND METHODS—A prospective, population-based study using retrospective observational data. We identified all 7,208 complete courses of treatment with nondrug therapy, sulfonylurea monotherapy, metformin monotherapy, and combination oral antihyperglycemic therapy between 1994 and 2002, inclusive, among members of the Kaiser Permanente Northwest Region. We calculated mean cumulative glycemic burden, defined as HbA1c-months >8.0 or 7.0% for each treatment. We then measured the likelihood that the next HbA1c would exceed 8.0 and 7.0% after HbA1c exceeded each of ten hypothetical treatment thresholds. Finally, we estimated multivariate logistic regression models to predict when HbA1c would continue to deteriorate. RESULTS—In this well-controlled population, the average patient accumulated nearly 5 HbA1c-years of excess glycemic burden >8.0% from diagnosis until starting insulin and about 10 HbA1c-years of burden >7.0%. Whenever patients crossed the American Diabetes Association-recommended treatment threshold of 8.0%, their next HbA1c result was as likely to be 8.0%. Multivariate prediction models had highly statistically significant coefficients, but predicted CONCLUSIONS—Clinicians should change glucose-lowering treatments in type 2 diabetes much sooner or use treatments that are less likely to fail. An action point at 7.0% or lower is more likely to prevent additional deterioration than the traditional action point of 8.0%.

441 citations


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01 Jan 2008
TL;DR: The use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events and identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes.
Abstract: Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standardtherapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

4,728 citations

Journal ArticleDOI
07 Nov 2007-JAMA
TL;DR: The prevalence of CKD in the United States in 1999-2004 is higher than it was in 1988-1994 and this increase is partly explained by the increasing prevalence of diabetes and hypertension and raises concerns about future increased incidence of kidney failure and other complications.
Abstract: ContextThe prevalence and incidence of kidney failure treated by dialysis and transplantation in the United States have increased from 1988 to 2004. Whether there have been changes in the prevalence of earlier stages of chronic kidney disease (CKD) during this period is uncertain.ObjectiveTo update the estimated prevalence of CKD in the United States.Design, Setting, and ParticipantsCross-sectional analysis of the most recent National Health and Nutrition Examination Surveys (NHANES 1988-1994 and NHANES 1999-2004), a nationally representative sample of noninstitutionalized adults aged 20 years or older in 1988-1994 (n = 15 488) and 1999-2004 (n = 13 233).Main Outcome MeasuresChronic kidney disease prevalence was determined based on persistent albuminuria and decreased estimated glomerular filtration rate (GFR). Persistence of microalbuminuria (>30 mg/g) was estimated from repeat visit data in NHANES 1988-1994. The GFR was estimated using the abbreviated Modification of Diet in Renal Disease Study equation reexpressed to standard serum creatinine.ResultsThe prevalence of both albuminuria and decreased GFR increased from 1988-1994 to 1999-2004. The prevalence of CKD stages 1 to 4 increased from 10.0% (95% confidence interval [CI], 9.2%-10.9%) in 1988-1994 to 13.1% (95% CI, 12.0%-14.1%) in 1999-2004 with a prevalence ratio of 1.3 (95% CI, 1.2-1.4). The prevalence estimates of CKD stages in 1988-1994 and 1999-2004, respectively, were 1.7% (95% CI, 1.3%-2.2%) and 1.8% (95% CI, 1.4%-2.3%) for stage 1; 2.7% (95% CI, 2.2%-3.2%) and 3.2% (95% CI, 2.6%-3.9%) for stage 2; 5.4% (95% CI, 4.9%-6.0%) and 7.7% (95% CI, 7.0%-8.4%) for stage 3; and 0.21% (95% CI, 0.15%-0.27%) and 0.35% (0.25%-0.45%) for stage 4. A higher prevalence of diagnosed diabetes and hypertension and higher body mass index explained the entire increase in prevalence of albuminuria but only part of the increase in the prevalence of decreased GFR. Estimation of GFR from serum creatinine has limited precision and a change in mean serum creatinine accounted for some of the increased prevalence of CKD.ConclusionsThe prevalence of CKD in the United States in 1999-2004 is higher than it was in 1988-1994. This increase is partly explained by the increasing prevalence of diabetes and hypertension and raises concerns about future increased incidence of kidney failure and other complications of CKD.

4,567 citations

Journal ArticleDOI
TL;DR: Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced, but awareness of the disorder remains low in many communities and among many physicians.

3,207 citations