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Biomedical subjects

D M Nathan

Publications and source records attributed to D M Nathan.

At least 55 records · Page 3Linked to original sources
PubMed1992

A prospective study of exercise and incidence of diabetes among US male physicians.

OBJECTIVE: To examine prospectively the association between regular exercise and the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: Prospective cohort study including 5 years of follow-up. PARTICIPANTS: 21,271 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years and free of diagnosed diabetes mellitus, myocardial infarction, cerebrovascular disease, and cancer at baseline. Morbidity follow-up was 99.7% complete. MAIN OUTCOME MEASURE: Incidence of NIDDM. RESULTS: At baseline, information was obtained about frequency of vigorous exercise and other risk indicators. During 105,141 person-years of follow-up, 285 new cases of NIDDM were reported. The age-adjusted incidence of NIDDM ranged from 369 cases per 100,000 person-years in men who engaged in vigorous exercise less than once weekly to 214 cases per 100,000 person-years in those exercising at least five times per week (P, trend, less than .001). Men who exercised at least once per week had an age-adjusted relative risk (RR) of NIDDM of 0.64 (95% Cl, 0.51 to 0.82; P = .0003) compared with those who exercised less frequently. The age-adjusted RR of NIDDM decreased with increasing frequency of exercise: 0.77 for once weekly, 0.62 for two to four times per week, and 0.58 for five or more times per week (P, trend, .0002). A significant reduction in risk of NIDDM persisted after adjustment for both age and body-mass index: RR, 0.71 (95% Cl, 0.56 to 0.91; P = .006) for at least once per week compared with less than once weekly, and P, trend, .009, for increasing frequency of exercise. Further control for smoking, hypertension, and other coronary risk factors did not materially alter these associations. The inverse relation of exercise to risk of NIDDM was particularly pronounced among overweight men. CONCLUSIONS: Exercise appears to reduce the development of NIDDM even after adjusting for body-mass index. Increased physical activity may be a promising approach to the primary prevention of NIDDM.

Adult↗
PubMed1992

Screening for diabetic retinopathy.

PURPOSE: To determine the appropriate patients, methods, and timing for screening for diabetic retinopathy. DATA SOURCES: Relevant articles were identified through prominent review articles, the authors' files, recommendations from experts, and a MEDLINE search (1986 to the present); additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Selection of articles on the natural history of retinopathy was limited to large clinical series and formal epidemiologic studies of defined populations. Selection of articles on the therapeutic effect of photocoagulation and of glycemic control was limited to randomized trials. Sources bearing on the accuracy of screening modalities were necessarily more varied. DATA EXTRACTION: For important variables, individual estimates from multiple studies are presented rather than a single meta-analytic summary estimate. RESULTS: Screening for retinopathy is justifiable if early detection leads to less vision loss at an acceptable cost. The evidence shows that 1) laser therapy reduces the rate of vision loss by 50% among patients with proliferative retinopathy and macular edema, conditions that are often asymptomatic; 2) duration of diabetes is the main risk factor for retinopathy; and 3) standard ophthalmoscopic examination has only moderate sensitivity (about 80% in research settings) and specificity (greater than 90% for proliferative retinopathy but lower for macular edema), making seven-field stereophotography a more accurate method. Estimates of cost effectiveness indicate that screening for retinopathy not only saves years of vision but may be cost saving from a societal perspective. CONCLUSIONS: Screening for retinopathy in patients with diabetes, and subsequent photocoagulation therapy for those who have high risk macular edema or proliferative retinopathy, is clearly beneficial.

Cost-Benefit Analysis↗
PubMed1992

Implementation of capillary blood glucose monitoring in a teaching hospital and determination of program requirements to maintain quality testing.

PURPOSE: To study the implementation of bedside capillary glucose monitoring using a hospital-wide quality control (QC) program. METHODS: A prospective study of QC performance in 7 outpatient and 39 inpatient treatment units was performed in a large teaching hospital over a 2-year period. Approximately 800 nurses were trained to perform bedside capillary glucose monitoring (Accu-Chek II, Boehringer-Mannheim, Indianapolis, IN). An eight-point QC program was instituted including proficiency testing, instrument maintenance, performance of daily controls, storage of reagent strips and supplies, instrument calibration, and documentation procedures. RESULTS: Comparison of laboratory and bedside test results (split-sample proficiency testing) revealed Y = 1.004X + 7.26, r = 0.95, with a mean percent difference of -4.2% (p < 0.001). Less than 7% of results fell outside +/- 20% of the laboratory results. QC scores (0 = worst to 4 = best), based on adherence to the QC program, improved from 0 on the first inspection to 3.7 +/- 0.17 by the 11th inspection. The most common QC deficiencies were failure to perform split-sample testing (41.4%) and failure to perform instrument maintenance (30.2%). Significant differences were noted in the QC performance of different types of medical services. During the 2-year study period, the total number of glucose assays performed in the clinical laboratories decreased by 22.2% concurrent with initiation of bedside testing. The number of instruments in the hospital increased from 10 to 46. CONCLUSIONS: Bedside capillary glucose assays can be widely implemented in large hospitals with an acceptable degree of accuracy. QC programs with frequent inspections are necessary to identify units that function inadequately, and a formal disciplinary policy is required to ensure compliance with the program.

Blood Glucose↗
PubMed1992

A prospective study of postmenopausal estrogen therapy and subsequent incidence of non-insulin-dependent diabetes mellitus.

The potential influence of postmenopausal estrogen therapy on the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM) is relatively unexplored, despite postulated effects of these hormones on glucose tolerance. We examined the association between postmenopausal hormone use and the subsequent incidence of NIDDM in a prospective cohort of 21,028 postmenopausal US women aged 30 to 55 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1976. During 12 years of follow-up (422,991 person-years), we confirmed 1249 cases of NIDDM. Current users of postmenopausal hormones had a relative risk of NIDDM of 0.80 (95% confidence interval, 0.67 to 0.96) as compared with never users, after adjustment for age and body mass index (BMI). Past users of these hormones had an age- and BMI-adjusted relative risk of 1.07 (0.93 to 1.23). These results were not materially altered by multivariate adjustment for age, BMI, family history of diabetes, and coronary risk factors. Comparable results were obtained when the analysis was restricted to symptomatic NIDDM as the outcome. We observed no appreciable modification of these associations by family history of diabetes or category of BMI. Duration of current or past use of postmenopausal hormones and dose of conjugated estrogen were not significantly related to incidence of NIDDM. Type of hormone (estrogen alone, progesterone alone, or combination) also did not appear to influence NIDDM risk. These prospective data indicate that postmenopausal hormone therapy is unlikely to be associated with a material increase in the incidence of NIDDM among women.

Adult↗
PubMed1992

Management of insulin-dependent diabetes mellitus.

Insulin therapy has been lifesaving for patients with insulin-dependent diabetes mellitus. Unfortunately, longer lifespan has unmasked microvascular, neurological and macrovascular complications that result in profound morbidity and increased mortality. Driven by the conviction that better physiological control of glycaemic levels will prevent and/or ameliorate long term complications, and by the desire to make diabetes care as user-friendly as possible, clinical research efforts have led to the development of new treatment methods with the aim of achieving near normal metabolic control. Such methods include the use of self monitoring, multiple daily insulin injection regimens, external and implantable insulin pumps, and whole organ pancreas and isolated islet cell transplantation. In addition, dietary manipulation, including the use of alpha-glucosidase inhibitors, has played a role in controlling glycaemia.

Blood Glucose↗
PubMed1992

Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study.

We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high-density lipoprotein cholesterol levels. In regression analyses that controlled for these and other potential risk factors, HbA1c remained significantly related to CVD among women. The relative odds of CVD increased 1.39-fold (95% confidence interval 1.06-1.83) for increases in HbA1c of 1% (e.g., for HbA1c from 5 to 6%). The relationship was not weakened when known diabetic subjects or subjects taking beta-blocker or thiazide medications were excluded from analysis. In contrast, there was no significant relationship between "casual" blood glucose and prevalent CVD. Our results reveal a strong, significant, independent association between hyperglycemia, measured by HbA1c, and CVD among older women.

Aged↗
PubMed1992

Insulinotropic action of glucagonlike peptide-I-(7-37) in diabetic and nondiabetic subjects.

OBJECTIVE: Whether glucagonlike peptide-I-(7-37) (GLP-I-[7-37]), a naturally occurring intestinal peptide, is insulinotropic in nondiabetic and non-insulin-dependent (type II) diabetic subjects. RESEARCH DESIGN AND METHODS: GLP-I-(7-37) or saline placebo was infused (1-5 ng.kg-1.min-1 for 30 min) in 4 nondiabetic and 11 type II diabetic subjects in the fasting and prandial state. Glucose, insulin, and GLP-I-(7-37) levels were measured. RESULTS: GLP-I-(7-37) infusion resulted in a 3- to 10-fold increase in peak insulin levels and in insulin area under the curve in nondiabetic and diabetic subjects. In diabetic subjects, infusion concurrent with a standard meal eliminated the postprandial glucose excursion for 60 min after the meal. Insulin-releasing potency of GLP-I-(7-37) was attenuated at decreased glucose levels. CONCLUSIONS: GLP-I-(7-37) has potent insulinotropic effects in nondiabetic and diabetic subjects. Whether GLP-I-(7-37) is useful as a therapeutic medication in type II diabetes requires further investigation.

Adult↗
PubMed1992

Clinical trial of programmable implantable insulin pump for type I diabetes.

OBJECTIVE: The first step in the evolution of an artificial pancreas is the development of a reliable implantable pump for insulin delivery. Despite recent advances, significant issues remain, including small size of studies and frequent irreversible catheter obstructions. We report safety, feasibility, and efficacy results from 56 patients, representing 73 patient-yr of pump experience, entered into a multicenter trial with a new implantable programmable pump. RESEARCH DESIGN AND METHODS: All patients had insulin-dependent (type 1) diabetes, were 38 +/- 8 yr old, and were not prone to severe hypoglycemia. The pump (Infusaid 1000) has a pulsatile mechanism powered by freon-vapor pressure. Its rate is regulated by battery-powered valves, operated via a hand-held programmer. The pump is refilled transcutaneously with 25 ml U100 insulin (Hoechst 21PH) on a monthly basis and has a second septum (side port) proximal to the catheter, which allows flushing the catheter or lavaging the pump unit. The pumps were implanted after 3 mo intensive subcutaneous insulin therapy and catheters were positioned either in the peritoneum (i.p., n = 38) or the superior vena cava (i.v., n = 18). RESULTS: All implanted pumps have functioned safely with no instance of overdelivery or stoppage. The most frequent complications were flow slow downs, presumably due to insulin precipitation within the pump, which occurred in 86% of pumps and were resolved in all but one case by lavaging the pump in situ with alkaline solution. Flow slow downs due to catheter obstruction occurred in 52% of the intravenous catheters but only 21% of the intraperitoneal catheters (P less than 0.05) and were resolved in all but two cases by diluent flushing through the sideport. Incidence of severe hypoglycemia decreased from 0.47 before implant to 0.05 episodes/patient-yr after pump implantation (P less than 0.001). Mean HbA1c fell from 7.4 +/- 1.2% after intensive subcutaneous therapy to 7.1 +/- 1.0% 12 mo after implantation. Only 2 patients withdrew from study after recurrent catheter problems, and quality-of-life questionnaires showed improvement in satisfaction with diabetes-specific quality of life when on implantable pump therapy. CONCLUSIONS: Insulin therapy with implantable pumps is effective and safe for periods up to 1.7 yr with a decreased risk of severe hypoglycemia than with intensive subcutaneous insulin therapy.

Adult↗
PubMed1992

The rationale for glucose control in diabetes mellitus.

After more than 60 years of active investigation, the role of intensive treatment regimens in preventing and ameliorating diabetes complications is close to being resolved. Currently available intensive regimens do not achieve normoglycemia and are associated with significant complications. Moreover, they are dependent on a high level of patient motivation and adherence and may not be widely applicable in the IDDM population. Given these limitations, it is critical that their benefit, if any, be documented before they are introduced widely into clinical therapy. If the glucose hypothesis proves to be true, the benefits of intensive therapy will outweigh all of its limitations. Although previous trials have failed to document benefits with regard to retinopathy (the decrease in the progression from incipient nephropathy to clinical proteinuria is of unknown clinical significance), the DCCT has adequate power to define the role of intensive therapy. If the DCCT demonstrates a salutary effect of intensive therapies, a rationale for such efforts finally will have been established. The goal for the next generation of clinical investigation will be to develop new means of intensive therapy that have less risk and are more accessible and acceptable to all persons with diabetes.

Animals↗
PubMed1991

Long-term metabolic and quality of life results with pancreatic/renal transplantation in insulin-dependent diabetes mellitus.

Evaluation of whole-organ pancreas transplantation in the therapy of IDDM has been difficult because of generally poor graft survival and significant complications in past experience. We report a technically successful simultaneous pancreas/kidney transplant program with patient and graft survival of 85% over 3 years of follow-up (mean 21 months) in 33 subjects with IDDM. Glucose metabolism was normalized without need for exogenous insulin immediately posttransplant in all but one recipient and remained normal in 85% of recipients. The outcome in pancreas/kidney recipients was compared with that in 18 insulin-dependent diabetic recipients of kidney transplant only performed in the same period. Quality of life was assessed with one general and one diabetes-specific questionnaire. General quality of life issues improved significantly in both pancreas/kidney and kidney recipients, but diabetes specific quality of life improved only in the pancreas/kidney recipients. Pancreas/kidney recipients required twice as long a period of hospitalization for the transplant and two times as many readmissions for a variety of complications. Only a minority of hospital admissions was strictly attributable to the pancreas graft. Of the five deaths in the pancreas/kidney recipients, two were attributable to the pancreas transplant. Pancreas transplantation in IDDM can now be accomplished with a high degree of success, resulting in normalized glucose metabolism and with overall mortality similar to kidney transplantation alone. Successful pancreas transplantation improves quality of life with respect to diabetes but this benefit is accomplished at a cost of increased hospital admissions and complications related to the transplanted pancreas. The effects of pancreas transplantation on the long-term complications of insulin-dependent diabetes remain unknown.

Adult↗
PubMed1991

Role of diabetologist in evaluating diabetic retinopathy.

OBJECTIVE: To evaluate the ability of diabetologists to screen diabetic patients for diabetic retinopathy. RESEARCH DESIGN AND METHODS: Comparison of eye examination performed by diabetologists with direct ophthalmoscopy through an undilated pupil and by ophthalmologists through a dilated pupil with seven-field stereoscopic fundus photography (gold standard). The study consisted of 67 insulin-dependent and non-insulin-dependent diabetic outpatients attending a diabetes clinic. RESULTS: On the basis of fundus photography, patients were classified as having no or insignificant (30%), minimal (31%), moderate (24%), or severe (15%) retinopathy. The diabetologists and ophthalmologists performed similarly in their ability to classify severity of diabetic retinopathy accurately. When no or insignificant retinopathy (isolated microaneurysms only) was detected by examination, clinically significant retinopathy detected by fundus photography was highly unlikely (less than 5%). On the other hand, if more than isolated microaneurysms were seen on examination, all examiners missed more severe lesions detected by fundus photography. Patients with corrected visual acuity worse than 20/30 had a high likelihood (100%) of moderate or severe retinopathy. CONCLUSIONS: Motivated well-trained diabetologists can screen for diabetic retinopathy. The absence of detectable lesions by direct ophthalmoscopy indicates that automatic referral to an ophthalmologist is not necessary. However, if any level of retinopathy is detected or corrected acuity is worse than 20/30, referral to an ophthalmologist is required. In this setting, fundus photography is advised because it is the most sensitive means of detecting clinically significant retinopathy. If other nonophthalmologists can be trained to achieve similar results, current recommendations for ophthalmologic referral that require annual ophthalmologic examinations for most diabetic patients may need to be reconsidered.

Adult↗
PubMed1990

Cognitive and affective disorders in elderly diabetics.

In non-insulin-dependent diabetes mellitus, performance of complex cognitive tasks requiring the storage and retrieval of new information is poorer than in age-matched controls. By contrast, performance of less demanding tasks such as immediate memory and simple reaction time is essentially equivalent for NIDDM patients and controls. This pattern parallels the cognitive change observed with normal aging, in which age differences are minimal on less demanding immediate memory tasks but older adults perform more poorly than young adults on secondary or long-term memory tasks. Age-related changes in cognitive performance have been attributed to a reduction in processing resources or working memory capacity. Although the explanation for NIDDM-related deficits remains to be identified, reduced glucose control and elevated levels of triglycerides appear to play some role in cognitive impairment. Non-insulin-dependent diabetes is associated not only with elevated levels of depression, but with an increased frequency of self-reported memory problems. Moreover, elevated levels of depression are associated with various indicators of neuropathy and with significant reductions in self-regulated control of glucose at the time of medical office visits. Diabetic patients may perceive less control over their lives as a result of the many restrictions associated with the disease. When provided with the opportunity to exercise control, however, performance on many cognitive tasks can be improved in NIDDM as well as in age-matched controls. This suggests that by providing NIDDM patients with opportunities to exercise increased control over their lives it may be possible to enhance motivation and to increase the likelihood of the patient's adopting more effective self-regulatory behaviors.

Aged↗
PubMed1990

Insulin treatment in the elderly diabetic patient.

Type II diabetes mellitus may affect as many as 20% of the elderly US population. In the absence of data to support the need to maintain a specific level of glucose beyond that necessary to relieve symptoms, choice of therapy is problematic. Clearly, supervised dietary therapy for the obese type II diabetic patient represents a safe and cost-effective treatment. For those patients who fail dietary therapy because they fail to lose weight or regain lost weight, or because blood glucose levels remain high despite weight loss, further therapy must be individualized. The only rational criteria for drug treatment supportable by currently available data are (1) persistent symptoms associated with hyperglycemia, (2) ketonuria in the unstressed state, and (3) certain cases of hyperlipidemia, especially with triglyceride levels greater than 1000 mg/dl. In these clinical settings, drug therapy is necessary to eliminate symptoms, prevent development of ketoacidosis, and reduce the risk of pancreatitis, respectively. Consideration of drug therapy should also be made in the case of very elevated blood glucose levels, even in the absence of symptoms, when dehydration and risk of severe hyperosmolarity exist. The issues regarding insulin versus sulfonylureas have not been examined specifically in the elderly population. Extrapolating from published studies that generally include patients older than 65 years leads to the following conclusions: Caution regarding adverse side effects of insulin (hypoglycemia, theoretic risk of hyperinsulinemia) and sulfonylureas (hypoglycemia, drug interactions, increased risk of cardiovascular death) must be balanced against the theoretic benefit of treatment in the absence of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Tests of glycemia in diabetes mellitus. Their use in establishing a diagnosis and in treatment.

PURPOSE: To assess the usefulness of urine glucose testing, physician-based and self blood glucose monitoring, and assays of glycated hemoglobin in diagnosing and treating diabetes mellitus. DATA IDENTIFICATION: Relevant literature in English from 1957 through early 1988 was identified via textbooks, original research articles, and review and policy papers, supplemented by a computer-based search of the National Library of Medicine MEDLINE database. STUDY SELECTION: Articles were selected because of prominence, based on frequent citation or policy authoritativeness, and relevance to the epidemiologic and clinical constructs of this paper. RESULTS: We analyze the epidemiologic studies underlying the higher diagnostic glycemic thresholds for diabetes proposed by the National Diabetes Data Group and we suggest a diagnostic strategy in which glycated hemoglobin may substitute for glucose tolerance testing. Our section on treatment stresses matching the intensiveness of hypoglycemic therapy with the intensiveness of monitoring: emphasizing the role of self blood glucose monitoring. Our findings and recommendations are summarized in the figures and tables. CONCLUSIONS: Major advances in the diagnosis and management of diabetes have been made in the past 10 years. In particular, an array of epidemiologic studies have provided a logical basis for diagnostic standards, and two new means of assessing glycemia--glycated hemoglobin and self-monitoring of blood glucose--have become widely available. These tests allow more convenient approaches to diagnosis, and provide a fuller description of glycemia, permitting more informed and intensive therapy.

Blood Glucose↗
PubMed1989

Diabetic myocardial infarction. Interaction of diabetes with other preinfarction risk factors.

To assess the effect of diabetes on outcome after acute myocardial infarction (MI), we compared a cohort of 228 type II (non-insulin-dependent) diabetic patients who had sustained acute MI with a similar number of nondiabetic patients with MI. Thirty-day mortality was greater in the diabetic group (27 vs. 17%). However, diabetic patients were older and had more cardiovascular disease before MI. Analyses accounting for such baseline risk revealed a complex effect of diabetes. The relative risk (RR) of dying from MI due to diabetes was greatest among patients with lowest baseline risk (RR 7.3) and least among those at highest baseline risk (RR 0.83). These effects were most striking with transmural MI, which was highly lethal for those with diabetes. Analyses with pulmonary edema as the endpoint support the significant risk conferred by diabetes and its interaction with baseline risk. Diabetes is a risk factor for poor outcome after MI, particularly among patients whose pre-MI cardiovascular status otherwise appears normal.

Aged↗
PubMed1988

Screening for diabetes mellitus.

Diabetes mellitus in nonpregnant adults is a chronic affliction that leads to significant vascular and neuropathic disease. Diabetes during pregnancy can lead to perinatal complications. Both of these types of diabetes are common, often asymptomatic, and readily diagnosable by glucose tolerance testing. As a result, screening can identify many previously undiagnosed patients. However there is only limited evidence that screening results in net therapeutic benefit. In the case of gestational diabetes, controlled trials indicate that hypoglycemic therapy decreases the frequency of macrosomia, but has no effect on perinatal mortality. Our analyses indicate that screening for gestational diabetes is a low-cost intervention that produces a small expected benefit. Screening for diabetes in the nonpregnant adult (almost always a type II diabetic) is not recommended, because the link between improving glucose control and reducing diabetic complications is currently too weak. Screening might be reasonable for particular patients, for example, obese persons who would be spurred to lose weight by a demonstration of glucose intolerance. Screening for type I diabetes followed by immunomodulating therapy is still too experimental for confident analysis.

Cost-Benefit Analysis↗