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Biomedical subjects

A L Peters

Publications and source records attributed to A L Peters.

At least 19 recordsLinked to original sources
PubMed2001

Using thiazolidinediones: rosiglitazone and pioglitazone in clinical practice.

Type 2 diabetes is a disorder that has numerous components, including insulin resistance, an insulin secretory defect, and an increase in hepatic glucose production. Until recently, only the insulin secretory defect could be treated. Within recent years, the thiazolidinedione (TZD) class of drugs, which targets primarily insulin resistance, was released. Originally developed in Japan as triglyceride-lowering agents, TZDs were found to be more effective in lowering blood glucose levels instead. The actions of 2 TZDs--rosiglitazone and pioglitazone--are discussed, and their glucose- and nonglucose-lowering effects are explained. Four case histories are presented to illustrate various patients' responses to TZDs in clinical practice. Although TZDs have been demonstrated to be effective in dealing with many different aspects of type 2 diabetes, further study, involving multiple clinical trials, is needed.

Adult↗
PubMed2000

Glycation impairs high-density lipoprotein function.

AIMS/HYPOTHESIS: To examine the effects of incubation of high-density lipoprotein (HDL) under hyperglycaemic conditions on several functions of HDL in vitro. METHODS: Human HDL (5 mg protein) was incubated for 1 week at 37 degrees C in the presence or absence of 25 mmol/l glucose. Additional samples of human HDL were incubated in butylated hydroxytoluene to control for oxidation. RESULTS: High-density lipoprotein incubated for 1 week in 25 mmol/l glucose had significant increases in the glycation product, fructoselysine and in the advanced glycation end product, N epsilon-(carboxymethyl)-lysine. High-density lipoprotein apolipoprotein AI and AII concentrations were not altered but glycated HDL had a 65% reduction in paraoxonase enzymatic activity. Glycated HDL did not inhibit monocyte adhesion to human aortic endothelial cells in response to oxidised low-density lipoprotein in vitro (43 +/- 4 monocytes bound vs 21 +/- 2 monocytes for control HDL, p < 0.0001). Hepatic lipase-mediated non-esterified fatty acid release from HDL lipids was enhanced in glycated HDL compared with control HDL (25 +/- 1 vs 16 +/- 1 nmol non-esterified fatty acid hydrolysed/min, respectively, p < 0.0001). Direct glycation of purified paraoxonase protein by incubation in 25 mmol/l glucose caused a 40% reduction in enzymatic activity. This glycated paraoxonase did not inhibit monocyte adhesion to human aortic endothelial cells in vitro (68 +/- 3 monocytes vs 49 +/- 2 monocytes bound for control paraoxonase, respectively, p < 0.001). We also measured a 40% reduction in paraoxonase activity in patients with Type II (non-insulin-dependent) diabetes mellitus and documented coronary artery disease compared with non-diabetic subjects, p < 0.0001. CONCLUSIONS/INTERPRETATION: Alterations in function of HDL caused by exposure to hyperglycaemic conditions could contribute to the accelerated atherosclerosis observed in Type II diabetes.

Aorta↗
PubMed2000

Revisiting the oral glucose tolerance test criterion for the diagnosis of diabetes.

OBJECTIVE: The Expert Committee on the Diagnosis and Classification of Diabetes retained the 2-hour glucose concentration on an oral glucose tolerance test of >/=11.1 mmol/L (200 mg/dL) as a criterion to diagnose diabetes. Since glycated hemoglobin levels have emerged as the best measure of long-term glycemia and an important predictor of microvascular and neuropathic complications, we evaluated the distribution of hemoglobin A1C (Hb A1C) levels in individuals who had undergone an oral glucose tolerance test to determine how well 2-hour values could identify those with normal versus increased Hb A1C levels. DESIGN: A cross-sectional analysis of 2 large data sets was performed. We cross-tabulated 2-hour glucose concentrations on an oral glucose tolerance test separated into 4 intervals (<7.8 mmol/L [140 mg/dL], 7.8-11.0 mmol/L [140-199 mg/dL], 11.1-13.3 mmol/L [200-239 mg/dL], and >/=13.3 mmol/L [240 mg/dL]) with Hb A1C levels separated into 3 intervals (normal; <1% above the upper limit of normal; and greater than or equal to the upper limit of normal + 1%). RESULTS: Approximately two thirds of patients in both data sets with 2-hour glucose concentrations of 11.1 to 13.3 mmol/L (200-239 mg/dL) had normal Hb A1C levels. In contrast, 60% to 80% of patients in both data sets with 2-hour glucose concentrations >/=13.3 mmol/L (240 mg/dL) had elevated Hb A1C levels. CONCLUSION: Since Hb A1C levels are the best measures presently available that reflect long-term glycemia, we conclude that the 2-hour glucose concentration criterion on an oral glucose tolerance test for the diagnosis of diabetes should be raised from >/= 11.1 mmol/L (200 mg/dL) to >/= 13.3 mmol/L (240 mg/dL) to remain faithful to the concept that diagnostic concentrations of glucose should predict the subsequent development of specific diabetic complications (e.g., retinopathy).

Blood Glucose↗
PubMed2000

The clinical implications of insulin resistance.

Insulin resistance is a prime risk factor associated with atherosclerosis and thrombosis. Other risk factors include dyslipidemia, obesity, and hypertension. The constellation of those factors, which is known as the cardiovascular dysmetabolic syndrome, increases the risk of macrovascular disease. Insulin resistance may contribute directly to cardiovascular disease and may also act as a precursor of diabetes, which is also associated with an increased risk of macrovascular disease. Insulin resistance can be difficult to assess clinically, but it is invariably present in patients with type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance. Treatment of insulin resistance includes diet, exercise, smoking cessation, strict control of hypertension, aggressive treatment of lipid abnormalities, and keeping the hemoglobin A1c level below 7%. New oral agents improve glycemic control for those with diabetes or insulin resistance, but their role in reducing the risk of macrovascular disease is undetermined.

Adult↗
PubMed1999

Relationship between fasting plasma glucose and glycosylated hemoglobin: potential for false-positive diagnoses of type 2 diabetes using new diagnostic criteria.

CONTEXT: New criteria for the diagnosis of type 2 diabetes mellitus have recently been introduced that lowered the diagnostic fasting plasma glucose (FPG) concentration from 7.8 to 7.0 mmol/L (140 to 126 mg/dL). OBJECTIVE: To determine if individuals with diabetes diagnosed by the new FPG concentration criterion would have excessive glycosylation (elevated hemoglobin [HbA1c] levels). DEFINITIONS: We determined the distribution of HbA1c levels in individuals using 4 classifications: (1) normal by the new criterion (FPG concentration <6.1 mmol/L [110 mg/dL]); (2) impaired fasting glucose by the new criterion (FPG concentration of 6.1-6.9 mmol/L [110-125 mg/dL]); (3) diabetes diagnosed solely by the new FPG concentration criterion of 7.0 through 7.7 mmol/L (126-139 mg/dL); and (4) diabetes diagnosed by the previous FPG concentration criterion of 7.8 mmol/L (140 mg/dL) or higher. DESIGN: Cross-sectional analysis of 2 large data sets (NHANES III and Meta-Analysis Research Group [MRG] on the Diagnosis of Diabetes Using Glycated Hemoglobin) that contained individuals in whom FPG concentrations, 2-hour glucose concentrations using an oral glucose tolerance test, and an HbA1c level were simultaneously measured. We cross-tabulated FPG concentrations (<6.1 mmol/L [110 mg/dL], 6.1-6.9 mmol/L [110-125 mg/dL], 7.0-7.7 mmol/L [126-139 mg/dL], and > or =7.8 mmol/L [140 mg/dL]) and HbA1c levels separated into 3 intervals: normal, less than the upper limit of normal (ULN); slightly elevated, ULN to ULN plus 1%; and high, higher than ULN plus 1%. RESULTS: Among subjects with normal FPG concentrations, HbA1c levels in the NHANES III (and the MRG) data sets were normal in 97.3% (96.2%), slightly elevated in 2.7% (3.6%), and high in 0.1% (0.2%). Among individuals with impaired fasting glucose, HbA1c concentrations were normal in 86.7% (81.4%), slightly elevated in 13.1% (16.4%), and high in 0.2% (2.2%). Among diabetic patients diagnosed by the new FPG criterion only, HbA1c levels were normal in 60.9% (59.6%), slightly elevated in 35.8% (32.8%), and high in 3.4% (7.6%). In diabetic patients diagnosed by the former FPG criterion, HbA1c levels were normal in 18.6% (16.7%), slightly elevated in 32.5% (21.0%), and high in 48.9% (62.3%). CONCLUSIONS: About 60% of the new cohort of diabetic patients in both data sets have normal HbA1c levels. We believe that diabetes should not be diagnosed in those with FPG concentrations less than 7.8 mmol/L (140 mg/dL) unless excessive glycosylation is evident. Individuals without excessive glycosylation but with moderate elevations of FPG concentrations (6.1-7.7 mmol/L [110-139 mg/dL]) should be diagnosed as having impaired fasting glucose and treated with an appropriate diet and exercise. This diagnostic labeling achieves the goal of early intervention without subjecting these persons to the potentially negative insurance, employment, social, and psychological consequences of a diagnosis of diabetes mellitus.

Adult↗
PubMed1998

The new diagnostic criteria for diabetes: the impact on management of diabetes and macrovascular risk factors.

The American Diabetes Association (ADA) has recently revised the system of classification and criteria for diagnosis of diabetes to help remedy the problem of undiagnosed diabetes, as well as to move away from a system of diagnosis based on treatment used toward a system based on disease etiology. The ADA report identifies 4 major categories of diabetes: (1) type 1 (absolute insulin deficiency); (2) type 2 (insulin resistance with an insulin secretory defect); (3) other specific types; and (4) gestational diabetes mellitus. The major changes are establishing a fasting glucose > or = 126 mg/dL for the diagnosis of diabetes and the suggestion that oral glucose tolerance tests are not needed in routine practice for the diagnosis of diabetes. The report stresses that the degree and type of diabetes can change over time and underscores the importance of early recognition and management of glycemic disorders. More aggressive screening, using fasting plasma glucose (FPG) concentrations of > or = 110 mg/dL as a marker of insulin resistance, should help identify not only patients with hyperglycemia but also those with insulin resistance without significant hyperglycemia. Even if hemoglobin A1c levels are in the normal range, patients in this category are at increased risk for developing macrovascular complications and may benefit from active intervention to reduce cardiac risk factors.

Blood Glucose↗
PubMed1998

Application of a diabetes managed care program. The feasibility of using nurses and a computer system to provide effective care.

OBJECTIVE: Treatment of patients with diabetes often falls short of recommended process and outcome guidelines. To improve the quality of the provided diabetes care, a program (the Comprehensive Diabetes Care Service [CDCS]) using a computerizing tracking and recall system in conjunction with nurses following protocols was implemented in a managed care setting. The impact of this program was studied and compared to the care provided to patients in another managed care setting. RESEARCH DESIGN AND METHODS: Patients followed in the CDCS who completed a diabetes education course were compared with patients followed in a group model health maintenance organization (GMH) who also completed a diabetes education course. CDCS patients received routine care in the program. GMH patients came to the CDCS yearly to have a diabetes evaluation. A chart review was also performed on their GMH outpatient records. RESULTS: Initial HbA1c levels were higher in the CDCS group than in the GMH group (median of 11.9 vs. 10.0%). In the CDCS patients, HbA1c levels not only fell significantly but were also significantly lower (P < 0.05) than in the GMH patients during the 2nd and 3rd year of follow-up care. There were no significant changes in HbA1c levels in the GMH patients. When CDCS patients were divided into compliant and noncompliant patients, the median HbA1c levels in compliant patients was 8.2%, compared with 11.5% in the noncompliant group. The CDCS patients who needed treatment for hypercholesterolemia were more likely to have a lowering of their cholesterol levels than the GMH patients. All process measures, such as yearly measurement of HbA1c levels, lipid levels, and foot and retinal exams, occurred much more frequently in the CDCS patients. CONCLUSIONS: The system developed and implemented for managing diabetes improved both outcome and process measures. The comparison group, followed at another managed care setting, received the care consistent with the average (suboptimal) quality of care provided to patients with diabetes in the U.S. Therefore, by using innovative systems of management, the treatment of patients with diabetes can be greatly improved.

Adult↗
PubMed1997

An overview of metformin in the treatment of type 2 diabetes mellitus.

Type 2 diabetes mellitus results from impaired insulin secretion and reduced peripheral insulin sensitivity. Treatment options include diet, oral antihyperglycemic agents, and insulin. Metformin, an oral biguanide, ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production. Unlike sulfonylureas, it does not stimulate insulin secretion, aggravate hyperinsulinemia, or cause hypoglycemia or weight gain (weight stabilizes or decreases). It also has beneficial effects on serum lipid profiles. In lean or overweight type 2 diabetic patients uncontrolled by diet, metformin monotherapy significantly improves glycemic control, compared with placebo, and to similar extents as sulfonylurea monotherapy. In secondary sulfonylurea failure, combination metformin-sulfonylurea treatment significantly improves glycemic control beyond that achieved with either agent along. Metformin-sulfonylurea also appears to be as effective as insulin or insulin plus sulfonylurea, suggesting that such combination therapy may obviate or substantially delay insulin therapy. Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure. Gastrointestinal side effects are common, but usually tolerated. Lactic acidosis risk is minimal, provided that contraindications, particularly renal impairment, and prescribing guidelines are respected. Aside from elevated plasma metformin levels with cimetidine and synergistic hypoglycemia with sulfonylureas, few interactions occur. Thus, metformin is safe and effective both as monotherapy or in combination with other antihyperglycemic agents in type 2 diabetic patients requiring additional glycemic control and may be advantageous when weight control is desirable and/or hyperlipidemia exists.

Diabetes Mellitus, Type 2↗
PubMed1997

An intervention for enhancing compliance with screening recommendations for diabetic retinopathy. A bicoastal experience.

OBJECTIVE: To determine whether an intervention at both the provider and patient level can increase the utilization of diabetic retinal examination among diabetic patients and to compare the results from a comparable study conducted on the East Coast. RESEARCH DESIGN AND METHODS: For the regional intervention study, all diabetic patients 18 years or older who enrolled in a large network-based health maintenance organization (HMO) in California were identified (n = 19,397). The identified diabetic patients received educational materials and a notification of their prior diabetic retinal examination status. Also, their primary care physicians received the current American Diabetes Association (ADA) guidelines for dilated retinal examinations and a list of patients due for diabetic retinal examination. RESULTS: There were 25 and 27% increases in the percentage of diabetic patients who received diabetic retinal examinations in 1995 compared with the percentages in 1993 and 1994, respectively. The increase in diabetic retinal examinations was most significant after the intervention (odds ratio = 1.4). Furthermore, the improvements in compliance after the intervention were almost identical between the studies implemented on the East and West Coasts. CONCLUSIONS: This study and the prior study demonstrate that such a "reminder" intervention can improve compliance with diabetic retinal screening recommendations. A generalizable intervention, such as this, may be applicable on a national level. For these programs to be successful, however, HMOs and physicians must have a collaborative relationship.

Adolescent↗
PubMed1996

A clinical approach for the diagnosis of diabetes mellitus: an analysis using glycosylated hemoglobin levels. Meta-analysis Research Group on the Diagnosis of Diabetes Using Glycated Hemoglobin Levels.

OBJECTIVE: To determine whether a glycosylated hemoglobin level can be used in place of an oral glucose tolerance test (OGTT) to diagnose diabetes. DATA SOURCES/STUDY SELECTION: An augmented MEDLINE search was performed to identify all reports from 1966 through June 1994 in which glycosylated hemoglobin levels were measured concurrently with performance of OGTTs in the same study. The corresponding authors were contacted and asked to provide individual data for all subjects tested. A total of 31 investigators representing 34 possible studies responded, and 18 were able to provide us with the data requested. Overall fasting plasma glucose concentrations, 2-hour postdextrose glucose concentrations, and glycosylated hemoglobin levels were available from 11 276 individuals. DATA EXTRACTION: To define normal glucose tolerance, impaired glucose tolerance (IGT), and diabetes, modified World Health Organization criteria were used. DATA SYNTHESIS: An analysis of the methods used for measurement of glycosylated hemoglobin levels revealed that the HbA1c assay showed the least variance in normal subjects. Therefore, only data from the 8984 subjects who had HbA1c levels measured were used. When we used the mean HbA1c level plus 4 SDs as a cutpoint, the sensitivity was 36% and specificity was 100% compared with the results of the OGTT. Because of the lack of agreement between OGTT results and HbA1c levels, models were created to analyze the distribution of HbA1c levels in each study. Using these models, we identified 3 subpopulations. The third subpopulation was likely to represent subjects with diabetes. When we applied an HbA1c level of 7.0% as a cutpoint, the sensitivity was 99.6% for the third subpopulation. When this cutpoint was reapplied to the OGTT results, of those subjects with an HbA1c level of at least 7.0%, 89% had diabetes, 7% had IGT, and 4% were normal. CONCLUSIONS: Although the OGTT is the "gold standard" for diagnosing diabetes, it is known to be poorly reproducible and is often not performed. Not only is use of an HbA1c level to diagnose diabetes more convenient, but therapeutic decisions are based on this value, regardless of the findings on the OGTT. An HbA1c level of 7.0% or higher often requires pharmacological intervention and is most often associated with the diagnosis of diabetes by World Health Organization standards. An HbA1c level below 7.0% would generally be treated with diet and exercise, regardless of the diagnosis of IGT or diabetes by OGTT. Thus, measurement of HbA1c levels may represent a reasonable approach to identifying treatment-requiring diabetes.

Diabetes Mellitus↗
PubMed1996

Maximal dose glyburide therapy in markedly symptomatic patients with type 2 diabetes: a new use for an old friend.

No consensus exists as to the best approach for treating markedly symptomatic patients with new-onset (or diet-treated) type 2 diabetes. Therefore, based on the experience of one successful case, further studies were undertaken to determine the safety and efficacy of maximal dose glyburide (10 mg, twice daily, in patients < 65 yr of age) or half the dose (10 mg, daily, in patients > or = 65 yr of age) for treating these patients. Fifty-five patients with polyuria, polydipsia, nocturia, involuntary weight loss, and blood glucose concentrations of 300 mg/dL or greater were treated following protocols that used maximal dose ( < 65 yr of age) or half-maximal dose ( > or = 65 yr of age) sulfonylurea agent therapy. Data were collected retrospectively in 30 patients and prospectively in 25. Patients in the prospective group differed only in that more laboratory measurements were obtained, and less strict guidelines for using insulin were adopted. Data were collected in both groups at baseline and 1 week and 4 months after starting the sulfonylurea agent therapy. Patients responded rapidly with a fall in blood glucose levels from 456 +/- 12 mg/dL at baseline to 202 +/- 10 mg/dL at 1 week to 120 +/- 5 mg/dL at 4 months. Glycated hemoglobin levels fell from 18.1 +/- 0.4% at baseline to 8.1 +/- 0.2% ( P < 0.0001) at 4 months. Most patients had symptomatic improvement within 3 days. Seventeen patients had positive (small or larger) urinary ketones, and 5 had positive serum ketones. Insulin to glucose and C peptide to glucose ratios improved maximally at 1 week, indicating rapid reversal of glucotoxicity on the beta-cell. At 4 months, 11 patients were receiving diet therapy alone, 29 were receiving submaximal dose sulfonylurea agent therapy, 6 remained on maximal dose sulfonylurea agent therapy, and only 3 were receiving insulin therapy. Six patients were lost to follow-up. No patient experienced hypoglycemia in the first 2 weeks of treatment. Maximal dose sulfonylurea agent therapy is a safe and effective method for treating patients with markedly symptomatic type 2 diabetes. Patients improve rapidly and are able to avoid the immediate institution of long term insulin therapy.

Adolescent↗
PubMed1996

Quality of outpatient care provided to diabetic patients. A health maintenance organization experience.

OBJECTIVE: To document the quality of diabetes care provided to patients in a large health maintenance organization (HMO) from 1 January 1993 to 1 January 1994 and compare it to the standards of the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS: To meet a Health Plan and Employer Data Information Set (HEDIS) requirement, a major HMO in California identified 14,539 members with diabetes and randomly selected 384 individuals for review. Charts were available on 353 of these patients, and after obtaining the information for the HEDIS review, additional information was extracted from the charts by an outside chart reviewer. This data set was used for an analysis of the quality of diabetic care provided by the participating medical groups to these HMO members during 1 year. Documentation of follow-up and measures of glycemic and lipid control was examined both for absolute values and for the frequency of measurement over the year. These results were compared to the ADA standards of care. RESULTS: Although patients averaged 4.5 visits to their primary care physicians (PCPs) over the year, 21% had one or fewer visits per year. Glycated hemoglobin levels were not documented in 56% of patients (ADA recommends two to four measurements per year), and of those with a glycated hemoglobin level measured. 39% had at least one value > or = 10%. Fasting plasma glucose concentrations were not documented in 65% of patients (four to six per year recommended). Foot exams (which should be performed at each regular visit) were not documented for 94% of patients. Urine protein measurements were not performed in 52% of patients. Additionally, many patients had elevated and untreated lipid abnormalities. CONCLUSIONS: In spite of the frequency of PCP visits during the year for many of these patients, diabetes management was inadequate. This lack of adequate preventive care will lead to an increased risk of the development of the acute and chronic complications of diabetes, creating an even greater future burden on the health care system and negative consequences for patients.

Body Weight↗