Development of glucagon sensitivity in neonatal rat liver.

The ontogenesis of the hepatic glucagon-sensitive adenylate cyclase system has been studied in the rat. With a partially purified liver membrane preparation, fetal adenylate cyclase was less responsive to glucagon than the enzyme from neonatal or adult livers. Similar results were obtained in gently prepared liver homogenates, suggesting that destruction of essential components of the fetal liver membrane did not account for the relative unresponsiveness of the adenylate cyclase enzyme to glucagon. Investigation of other factors that might account for diminished fetal hepatic responsiveness to glucagon indicate (a) minimal glucagon degradation by fetal membranes relative to 8-day or adult tissue; and (b) available adenylate cyclase enzyme, as suggested by a 13-fold increase over basal cyclic AMP formation with NaF in fetal liver membranes. These results indicate that neither enhanced glucagon degradation nor adenylate cyclase enzyme deficiency accounts for the relative insensitivity of the fetal hepatic adenylate cyclase system to glucagon. In early neonatal life, hepatic adenylate cyclase responsiveness to glucagon rapidly developed and was maximal 6 days after birth. These changes were closely paralleled by a fivefold increase in glucagon binding and the kinetically determined Vmax for cyclic AMP formation. These observations suggest that (a) fetal hepatic unresponsiveness to glucagon may be explained by a limited number of glucagon receptor sites; (b) during the neonatal period, the development of glucagon binding is expressed primarily as an increase in adenylate cyclase Vmax; (c) the ontogenesis of hepatic responsiveness to glucagon may be important in the resolution of neonatal hypoglycemia.

Plasma vasopressin in uncontrolled diabetes mellitus.

Concentrations of the antidiuretic hormone, arginine vasopressin, were measured in 28 patients with severe hyperglycemia to determine if abnormalities in hormonal regulation of water excretion could contribute to the extreme dehydration of uncontrolled diabetes mellitus. Vasopressin levels were markedly elevated in both nonketotic and ketotic patients, indicating that vasopressin deficiency plays no role in the polyuria that accompanies hyperglycemia. Instead, the observed increases in vasopressin represent an ineffective effort to conserve water in the face of an overwhelming solute diuresis caused by the glucosuria. The reasons for such marked elevations in plasma vasopressin in these diabetic patients are multifactorial. Both groups of diabetic patients had evidence of hypovolemia, which was sufficient in magnitude to stimulate vasopressin release. Furthermore, nausea provided an independent stimulus to vasopressin secretion in many patients. Osmotic stimulation might have resulted from the large fraction of unidentified plasma solutes, but this factor alone was not sufficient to explain the markedly increased concentrations of vasopressin. Whether such elevations in vasopressin could have metabolic and/or hemodynamic effects in uncrontrolled diabetes remains to be established.

Is diabetes a public-health disorder?

In the U.S., certain health conditions are readily accepted as "public-health disorders," and others continue to be primarily viewed as "clinical diseases." Reflecting on infectious conditions, it appears that disease burden, rapid change in disease incidence (suggesting preventability), and public concern about risk are three essential characteristics that define a public-health disorder. By any one of several criteria, diabetes is associated with a very high burden to individuals with the disease, as well as to society in general. Further, there is convincing and increasing evidence that primary, secondary, and tertiary prevention strategies are effective in reducing the disease burden associated with diabetes. Yet most would still consider diabetes primarily to be a clinical disease. In part, this perception is based on the fact that, in association with aging and a possible strong family history, diabetes and its complications may appear inevitable to many. Further, much of the burden associated with diabetes is insidious, coming on gradually only after a considerable number of years. Thus, the burden associated with diabetes has not dramatically increased in the past few months or years; it has been here for some time and is increasing steadily. Finally, our understanding of public concern is only now being systematically investigated. Factors that galvanize the public to demand societal or governmental action are quite complex and very different from those elements that convince the scientist/expert to request "public-health responses." Legitimate and important public-health dimensions associated with diabetes complement the critical role of clinical care. To effectively establish these public-health perspectives, public concern must be incorporated into efforts to define the burden of diabetes and our extant ability to prevent and thereby reduce this burden.

The public health burden of diabetes and the reality of limits.

Improvements in diabetes surveillance, diagnosis, and treatment have, in recent years, heightened awareness of the burden of diabetes and aroused concern about the amount of health care resources that will be necessary to manage this disease effectively in the future. Examination of diabetes from the twin perspectives of economics and public health challenges basic notions of the health care tradition in the Western world: the real-world combination of finite resources and the growing need/demand for health services forces the consideration of limits in the provision of health care. The growing need to rationally allocate limited health care resources poses emotional, potentially divisive questions of science, politics, economics, and ethics that patients and physicians must each address.

The role of footwear in the prevention of foot lesions in patients with NIDDM. Conventional wisdom or evidence-based practice?

OBJECTIVE: To conduct a prospective evaluation of footwear characteristics as predictors of diabetic foot wounds. RESEARCH DESIGN AND METHODS: A total of 352 patients with NIDDM enrolled in a randomized controlled trial aimed at preventing diabetic foot lesions in an academic general medicine practice were studied. Foot wounds (n = 63) were modeled univariately and multivariably using generalized estimating equations. The dependent variable was a wound classified as a 1.2 or greater according to the Seattle Wound Classification System, indicating at least a superficial or healing minor lesion with no functional interruption of the protective cutaneous barrier. Independent variables included detailed measures of style and material of patients' indoor and outdoor shoes, appropriate length and width, sock fibers, whether the patient had bought new shoes in the past 6 months, and if the patient had been recommended for special shoes. Modeling controlled for intervention status and physiological measures (baseline wound, monofilament abnormalities, and serum HDL level). RESULTS: Initial screening (P < 0.20) suggested that a recommendation for special shoes, shoe length, and shoe width were indicative of wounds at follow-up (odds ratios [ORs] 2.19, 1.84, 1.86, respectively), while having bought shoes in the past 6 months was associated with no wound at follow-up (OR 0.60). The final multivariable model included only the recommendation for special shoes (OR 2.19; 95% CI 1.07-4.49). CONCLUSIONS: Many variables commonly cited as protective measures in footwear for diabetic patients were not prospectively predictive when controlling for physiological risk factors. Rigorous analyses are needed to examine the many assumptions regarding footwear recommendations for diabetic patients.

Independent physiological predictors of foot lesions in patients with NIDDM.

OBJECTIVE: To identify and quantify independent physiological risk factors for foot lesions in diabetic patients. RESEARCH DESIGN AND METHODS: There were 352 patients enrolled in a 1-year randomized controlled trial aimed at reducing risks for lower-extremity pathology through patient education and system interventions. Inclusion criteria were as follows: being age 40 years or over, being at or above ideal body weight, and having been diagnosed with NIDDM. Participants were predominantly African-American (76%), elderly (mean 60 years of age), indigent (77% with annual income < +10,000), or women (81%) who had diabetes for 10 years. Prospective multivariate modeling used baseline clinical signs (e.g., blood pressure, dermatological characteristics, and neuropathic measures) and laboratory values (e.g., lipid profiles and measures of glycemic control) to predict foot lesions rated using the Seattle Wound Classification. RESULTS: When controlling for intervention effects, only measures of neuropathy (monofilament testing [odds ratio ¿OR¿ 2.75, 95% CI 1.55-4.88] and thermal sensitivity testing [2.18, 1.13-4.21]) predicted wounds classified 1.2 (minor injury), but investigation of wounds rated at least 1.3 (nonulcerated lesions) indicated baseline wounds (13.41), 3.19-56.26), monofilament abnormalities (5.23, 2.26-12.13), and low HDL (1.63, 1.11-2.39) as predictors. Although fungal dermatitis, dry cracked skin, edema, ingrown nails, microalbuminuria, fasting blood glucose, and hemoglobin A1c were candidates for one or both of the multivariable models (P < 0.3), they were not significant multivariate predictors. CONCLUSIONS: Lesions may be preventable with aggressive screening for peripheral neuropathy and abnormal lipids. Also, these results provide empirical support for the commonly held belief that foot lesions prospectively predict future wounds.

Alternative approaches to public health surveillance of IDDM.

OBJECTIVE: To assess the appropriateness of national surveillance of IDDM. RESEARCH DESIGN AND METHODS: We reviewed the structure and function of national disease surveillance, the diverse goals of IDDM surveillance, and prior experience with IDDM as a reportable disease. RESULTS: Surveillance is the systematic and ongoing collection, analysis, interpretation, and dissemination of data linked to public health action. The potential goals of surveillance of IDDM are to understand the etiology and trends in incidence of IDDM, to measure the burden of IDDM and its complications, and to assess mortality. Problems associated with surveillance of IDDM include underreporting, delayed reporting, and lack of funding. CONCLUSIONS: To make IDDM a nationally reportable disease is neither warranted nor feasible at this time. Although surveillance is needed to understand diabetes better and for diabetes control, proposed initiatives, such as major expansions of IDDM reporting, should be developed to address specific questions, problems, and needs--still recognizing real-world issues of competing priorities and limited resources.

Pregnancy following renal transplantation in a patient with insulin-dependent diabetes mellitus.

Renal transplantation and peritoneal or hemodialysis are therapeutic options increasingly available to diabetic patients with uremia. We report a patient with insulin-dependent diabetes mellitus (IDDM) and advanced retinopathy and nephropathy who had three pregnancies. Her first pregnancy resulted in a living female with Pierre-Robin syndrome and arthrogryposis. The second pregnancy, 8 mo post-kidney transplantation, necessitated a therapeutic abortion for an anencephalic fetus. Her third pregnancy, 22 mo after kidney transplantation, was associated with intensive diabetes management and resulted in delivery by cesarean section of a healthy boy. Renal and retinal function remained stable during both her second and third pregnancies. As more patients with IDDM achieve fertility post-renal transplantation, aggressive principles of diabetes regulation need to be expanded to include consideration of the interaction of the post-kidney-transplant state and diabetes mellitus during pregnancy.

The diabetes education study: a controlled trial of the effects of diabetes patient education.

The Diabetes Education Study (DIABEDS) was a randomized, controlled trial of the effects of patient and physician education. This article describes a systematic education program for diabetes patients and its effects on patient knowledge, skills, self-care behaviors, and relevant physiologic outcomes. The original sample consisted of 532 diabetes patients from the general medicine clinic at an urban medical center. Patients were predominantly elderly, black women with non-insulin-dependent diabetes mellitus of long duration. Patients randomly assigned to experimental groups (N = 263) were offered up to seven modules of patient education. Each content area module contained didactic instruction (lecture, discussion, audio-visual presentation), skill exercises (demonstration, practice, feedback), and behavioral modification techniques (goal setting, contracting, regular follow-up). Two hundred seventy-five patients remained in the study throughout baseline, intervention, and postintervention periods (August 1978 to July 1982). Despite the requirement that patients demonstrate mastery of educational objectives for each module, postintervention assessment 11-14 mo after instruction showed only rare differences between experimental and control patients in diabetes knowledge. However, statistically significant group differences in self-care skills and compliance behaviors were relatively more numerous. Experimental group patients experienced significantly greater reductions in fasting blood glucose (-27.5 mg/dl versus -2.8 mg/dl, P less than 0.05) and glycosylated hemoglobin (-0.43% versus + 0.35%, P less than 0.05) as compared with control subjects. Patient education also had similar effects on body weight, blood pressure, and serum creatinine. Continued follow-up is planned for DIABEDS patients to determine the longevity of effects and subsequent impact on emergency room visits and hospitalization.

Report of the health care delivery work group: behavioral research related to the establishment of a chronic disease model for diabetes care.

As one of four work groups for the November 1999 conference on Behavioral Science Research in Diabetes, sponsored by the National Institute on Diabetes and Digestive and Kidney Diseases, the health care delivery work group evaluated the status of research on quality of care, patient-provider interactions, and health care systems' innovations related to improved diabetes outcomes. In addition, we made recommendations for future research. In this article, which was developed and modified at the November conference by experts in health care delivery, diabetes and behavioral science, we summarize the literature on patient-provider interactions, diabetes care and self-management support among underserved and minority populations, and implementation of chronic care management systems for diabetes. We conclude that, although the quality of care provided to the vast majority of diabetic patients is problematic, this is principally not the fault of either individual patients or health care professionals. Rather, it is a systems issue emanating from the acute illness model of care, which still predominates. Examples of proactive population-based chronic care management programs incorporating behavioral principles are discussed. The article concludes by identifying barriers to the establishment of a chronic care model (e.g., lack of supportive policies, understanding of population-based management, and information systems) and priorities for future research in this area needed to overcome these barriers.

Diabetes trends in the U.S.: 1990-1998.

OBJECTIVE: To examine trends in diabetes prevalence in the U.S. RESEARCH DESIGN AND METHODS: This study was conducted via telephone surveys in states that participated in the Behavioral Risk Factor Surveillance System between 1990 and 1998. The participants consisted of noninstitutionalized adults aged 18 years or older. The main outcome measure was self-reported diabetes. RESULTS: The prevalence of diabetes rose from 4.9% in 1990 to 6.5% in 1998--an increase of 33%. Increases were observed in both sexes, all ages, all ethnic groups, all education levels, and nearly all states. Changes in prevalence varied by state. The prevalence of diabetes was highly correlated with the prevalence of obesity (r = 0.64, P<0.001). CONCLUSIONS: The prevalence of diabetes continues to increase rapidly in the U.S. Because the prevalence of obesity is also rising, diabetes will become even more common. Major efforts are needed to alter these trends.

Diabetes mellitus and cerebrovascular disease: prevalence of carotid artery occlusive disease and associated risk factors in 482 adult diabetic patients.

The prevalence of carotid artery occlusive disease (CAOD) in a population of adults with diabetes mellitus was determined, and factors associated with its presence were identified. By oculoplethysmography and phonoangiography, 20% of the population studied had detectable CAOD. Univariate analyses revealed that patients with CAOD had a higher prevalence of retinopathy proteinuria, a slower mean conduction velocity in two of three nerves tested, and more atherosclerosis in the leg arteries. Furthermore, increased age, higher cholesterol, lower fasting insulin, higher systolic blood pressure, and less adiposity were associated with the presence of CAOD. Sex, race, type of diabetes (type I or II), duration of diabetes, and measures of glycemia were not related to CAOD. When 10 variables were analyzed by multivariate methods, higher systolic blood pressure, higher cholesterol, and reduced adiposity were found to be the combination most significantly related to CAOD.

Trends in diabetes and diabetic complications, 1980-1987.

OBJECTIVE: Although diabetes is a major source of morbidity and mortality in the United States, only recently has a unified national surveillance system begun to monitor trends in diabetes and diabetic complications. RESEARCH DESIGN AND METHODS: We established a diabetes surveillance system using data for 1980-1987 from vital records, the National Health Interview Survey, the National Hospital Discharge Survey, and the Health Care Financing Administration's records to examine trends in the prevalence and incidence of diabetes, diabetes mortality, hospitalizations, and diabetic complications. RESULTS: From 1980 through 1987, the number of individuals known to have diabetes increased by 1 million--to 6.82 million. Age-standardized prevalence for diabetes increased 9% during this period, from 25.4 to 27.6/1000 U.S. residents (P = 0.03). The incidence of diabetes increased among women (P = 0.003), particularly among those greater than 65 yr old (P = 0.02). Age-standardized mortality rates (for diabetes as either an underlying or contributing cause) per 100,000 individuals with diabetes declined 12%, from 2350 to 2066. Annual mortality rates from stroke (as an underlying cause and diabetes as a contributing cause) and diabetic ketoacidosis declined 29% (P = 0.003) and 22% (P less than 0.001), respectively. During these 8 yr, hospitalization rates for major CVD and stroke (as the primary diagnoses and diabetes as a secondary diagnosis) increased 34% (P = 0.006) and 38% (P = 0.01), respectively. Also during this period, hospitalization rates increased 21% for diabetic ketoacidosis (P = 0.01) and 29% for lower-extremity amputations (P = 0.06). From 1982 through 1986, treatment for end-stage renal disease related to diabetes increased greater than 10% each year (P less than 0.001). The prevalence of diagnosed diabetes was nearly twice as high in blacks as in whites (P = 0.04). Blacks also had increased rates of lower-extremity amputation (P = 0.02), diabetic ketoacidosis (P less than 0.001), and end-stage renal disease (P = 0.01). CONCLUSIONS: Diabetes surveillance data will be useful in planning, targeting, and evaluating public health efforts designed to prevent and control diabetes and its complications.

Risk factors for coronary heart disease mortality among persons with diabetes.

Although coronary heart disease is a leading cause of morbidity and mortality among persons with diabetes, the risk factors for coronary heart disease have not been well established for this population. The authors performed a case-control analysis by using data from two large population-based surveys. Cases of persons who died of coronary heart disease were identified from the 1986 National Mortality Followback Survey, and controls were taken from behavioral risk factor surveys conducted in 35 states in 1988. Diabetic women younger than 55 years with no other risk factors for coronary heart disease had a 16-fold higher risk of dying from coronary heart disease than did women without diabetes. About one-third of younger women who died of coronary heart disease had diabetes. Diabetic men less than 45 years old with no other risk factors for coronary heart disease had an eightfold higher risk of coronary heart disease mortality. Among older white men and women, diabetes increased the risk of mortality from coronary heart disease about twofold. In younger diabetics, current cigarette smoking was associated with a 50% increase in risk, and high blood pressure increased the risk more than threefold. In the older age group, risk factors for coronary heart disease mortality were similar among those with and those without diabetes: Cigarette smoking and high blood pressure each were associated with about a twofold increase in risk. Diabetes is a particularly strong risk factor for mortality from coronary heart disease in young adults. Smoking and blood pressure control represent major opportunities to reduce the risk of coronary heart disease among persons with diabetes.

Recording of diabetes on death certificates. Has it improved?

OBJECTIVE: To determine whether the recording of diabetes on death certificates improved from 1986 to 1993. METHOD: Comparison of two National Mortality Follow-back Surveys that selected independent samples of death certificates with the purpose of obtaining information from informants about the decedents. RESULTS: The recording of diabetes on death certificates did not improve from 1986 to 1993. CONCLUSION: Periodic monitoring of the accuracy of death certificates is essential for proper interpretation of mortality statistics which are routinely used to describe the burden of diabetes in our society.

Diabetes mellitus and asthma: "twin" challenges for public health and managed care systems.

Many changes are rapidly occurring in and to health care systems in the United States. These changes reflect fundamental concerns about issues of access, quality of care, and cost of health services. The emergence of chronic diseases, the importance of economic considerations in health decisions; and the proper role of managed care organizations (MCOs) are of particular significance. Diabetes mellitus (DM) and asthma are two conditions that are frequently used as "model diseases" to study the impact of these changes. In spite of apparent differences between asthma and DM, there are, in fact, many important commonalities that explain the attention being directed to these diseases. In considering basic tenets, objectives, and approaches, MCOs and public health systems also have very common interests and characteristics. In understanding the impact of the many emerging health care concepts and approaches on DM and asthma, public health and MCOs can be better positioned not only to understand each other, but also to subsequently address other important chronic diseases, injury-related disorders, and behavioral/emotional conditions in an effective and efficient manner.

Diabetes--a common, growing, serious, costly, and potentially preventable public health problem.

An estimated 135 million people worldwide had diagnosed diabetes in 1995, and this number is expected to rise to at least 300 million by 2025. The number of people with diabetes will increase by 42% (from 51 to 72 million) in industrialized countries between 1995 and 2025 and by 170% (from 84 to 228 million) in industrializing countries. Several potentially modifiable risk factors are related to diabetes, including insulin resistance, obesity, physical inactivity and dietary factors. Diabetes may be preventable in high-risk groups, but results of ongoing clinical trials are pending. Several efficacious and economically acceptable treatment strategies are currently available (control of glycemia, blood pressure, lipids; early detection and treatment of retinopathy, nephropathy, foot-disease; use of aspirin and ACE inhibitors) to reduce the burden of diabetes complications. Diabetes is a major public health problem and is emerging as a pandemic. While prevention of diabetes may become possible in the future, there is considerable potential now to better utilize existing treatments to reduce diabetes complications. Many countries could benefit from research aimed at better understanding the reasons why existing treatments are under-used and how this can be changed.

Interdisciplinary and intersectoral approach: a challenge for integrated care.

Integrated care for health disorders, particularly chronic diseases, is a long-term and complex challenge, particularly because of the involvement of many individuals with different beliefs, attitudes, assumptions and reward structures. Two basic conceptual models of disease--the biomedical and psychosocial--underlie many of these differences. The biomedical model views humans as the sum of multiple individual 'subsystems,' and disease represents dysfunction of one or more of these subsystems. This model is 'reductionist' and 'individualistic' in nature in that if 'THE' defective subsystem can be identified, studied and improved, it is assumed that health would return. The biomedical model focuses primarily on the individual with ill-health and has added greatly to our basic understanding of disease processes. The psychosocial model is 'interactive' and dynamic, and sees the 'whole' as more than the sum of its parts. This model values elements outside of the individual, e.g. work and home environment, as important in maintaining or establishing health. Because of fundamental differences between these 2 models of health and disease, conflicts, e.g. efficacy vs. exposure; role of individual vs. environment; etc., may exist among varying professionals regarding the nature, purpose, targets, structure, and consequences of integrated care programs. These fundamental conflicts, if unrecognized and ignored, can significantly attenuate the benefits of well-intentioned prevention and treatment integrated care programs.

Economic impact of diabetes mellitus in the elderly.

Diabetes mellitus is a prevalent disease in Americans aged 65 years and older. It leads to significant morbidity, mortality, and utilization of health care services. Using extant data, we estimated that health care services provided to elderly persons with diabetes cost $5.16 billion annually, nearly 80% of which were attributed to hospital costs. Treatment for cardiovascular disease as a complication of diabetes accounted for the largest proportion of these costs. In addition to admissions for uncomplicated diabetes, substantial portions of inpatient costs were attributed to renal and neurologic diseases. Expenditures per capita for medical care were 50% higher in the elderly diabetic population than in an elderly nondiabetic population. The average yearly expenditure per diabetic patient was estimated to be $4265, $900 of which were out-of-pocket expenses. We conclude that increased vigilance to prevent or delay the incidence of morbidity leading to hospital admissions must take priority in caring for patients with DM. Intensifying outpatient care may offer the opportunity to accomplish this goal.

Strategies to improve diabetes care delivery.

Although the primary care office is an important location for integrating new advances in the treatment of diabetes, the current delivery of preventive primary care for patients with diabetes falls short of clinical recommendations. Barriers within the existing health care system, practice structure, and physician and patient support services are among the most commonly cited obstacles to initiating better preventive care. As public health groups demand greater accountability from the medical system, regulatory efforts focus more scrutiny on systems, clinic practices, and even individual physician practices. Although improving care delivery effectively and efficiently is difficult, strategies to exist that can increase the likelihood of improving patient outcomes. Successful diabetes initiatives are often characterized by the consensual adoption of an evidence-based treatment plan. Effective physician-oriented interventions include the use of reminder systems, local opinion leaders, and academic detailing. In addition, several national diabetes initiatives are likely to influence primary care practice. New measures of accountability will be widely used to determine the quality of primary diabetes care delivery.