Complications of IDDM and NIDDM

Epidemiology Of Diabetic Complications

Epidemiology Of Diabetic ComplicationsThe complications of diabetes mellitus continues to be a major source of morbidity and early mortality but have not yet been comprehensively studied from an epidemiological viewpoint. The prevalence, incidence and interrelationships between seven major complication states (i.e., death, proliferative retinopathy, microalbuminuria, overt nephropathy, renal failure, neuropathy, and coronary and lower extremity arterial disease of IDDM) and their risk factors are being examined in a 10-year prospective study of IDDM subjects diagnosed in childhood. Risk factors and complication status are determined on a biennial basis. The study population is a well-defined cohort of IDDM patients identified from the Children’s Hospital of Pittsburgh IDDM Registry shown to
be representative of the local county wide diabetic population.

Clinically, the possibility will be explored of more closely monitoring the disease using electronic communications. This type of intervention has already been tested in other cities across the nation with varying degrees of success. The compliance is the parameter that varies the success of an effort aimed at keeping the patients and their families in continuous contact with the clinician by the use of a personal computer. The advantage is that of having clinical advice rapidly at any time of the day (or the night) at an extremely low cost for the patient and for the medical provider.

Bypass Angioplasty Revascularization Investigation (BARI)

Recently, a new and extremely interesting aspect of the pathology of diabetes and its complications was revealed. BARI is a randomized international multicenter clinical trial that compares a strategy of initial percutaneous transluminal coronary angioplasty (PTCA) to that of initial coronary artery bypass graft (CABG) surgery for selected patients with multivessel coronary artery disease (CAD). The first tested hypothesis was that a strategy of initial PTCA is no worse than one of initial CABG, as assessed by mortality at five years. Other major endpoints included: myocardial infarction, need for repeat procedures and hospitalizations, symptomatic and functional status, radionuclide ejection fraction, quality of life and economic impact. The trial began in July 1987. Investigators from 14 primary and four satellite sites randomized 1,829 patients. In addition, 2,013 patients who were eligible but not randomized and a random sample of 422 patients deemed ineligible based on their angiogram were recruited into a registry. A central radiographic laboratory processes all angiographic data and a central EKG laboratory processes all resting and exercise EKGs.

On Sept. 21, 1995, the National Institutes of Health issued a medical alert to inform the medical community of the findings of the BARI trial with respect to the subgroups of patients on drug treatment for diabetes.

There are 14 million people with diabetes (diagnosed and undiagnosed) in the United States. Diabetes is a risk factor for coronary heart disease, which affects more than 13 million Americans. Sixty-five percent of those with diabetes die of some form of heart or blood vessel disease. More than 670,000 revascularization procedures were performed in the United States in 1993. Based on this number, approximately 300 patients who are similar to those of the BARI trial undergo either CABG or PTCA every day. About 60 of these patients are taking medication for diabetes. However, because BARI was not designed to study diabetics specifically, data that might be helpful in explaining this treatment difference are not yet available.

Under the auspices of University of Pittsburgh Diabetes Institute, it will be possible to go back to the patient charts to collect additional information that may shed light on the BARI findings. In addition, it will be possible to perform prospective studies, since the scientists will have access to a population of approximately 1,000 overweight adult patients, currently involved in the clinical research protocols of the Pittsburgh Obesity and Nutrition Research Center (ONRC). Almost all of the women who undergo CABG or PTCA interventions are diabetic patients, and many diabetic women are already enrolled in this program of the ONRC.

Childhood Depression-Nosologic/Development Aspects

Depression is the most common psychiatric morbidity in youths with IDDM, is often protracted, and is a risk factor for medical complications. However, there are no psychosocial interventions of proven effectiveness for this mental disorder in juveniles with IDDM. Thus, the goals of this project were to:

  • Modify an existing manual for treatment of depression in childhood called Contextual Psychotherapy (CP) to accommodate the IDDM, Test and refine the resultant manual with depressed diabetic youths (n=5),
  • Conduct a small-scale efficacy trial with depressed 8-to-16 year-old diabetic youths (n=40) using a randomized design and a “treatment as usual” control group, and
  • Arrive at a final psychotherapy protocol suitable for depressed youths with IDDM.

Neurobehavioral Complications in Type 1 Diabetic Adults

The medical complications of diabetes mellitus are well known. Damage to the small and large blood vessels appears to be associated with chronic hyperglycemia, and as a consequence, diabetic individuals have a greatly increased risk of developing retinopathy, nephropathy, neuropathy, and cardiovascular disease. One organ that has generally been ignored is the brain, yet an increasing number of reports have suggested that some diabetic individuals may show impairments on certain cognitive tests. We administered neuropsychological, information-processing, and psychosocial measures to 189 diabetic adults (21-49 years old), and 148 non-diabetic controls. While global cognitive deficits were generally not found, impairments were evident on psychomotor and visuospatial measures. The best predictor of impairment was chronic hyperglycemia, as indexed by a diagnosis of peripheral neuropathy. Our findings have led us to hypothesize that chronic hyperglycemia is associated with the development of a “white matter” disease.

We now plan to conduct three studies that include neuropsychological and psychosocial assessments, as well as physical examinations and laboratory measures. The first is a prospective study that tests the hypothesis that the subsequent occurrence (or worsening) of certain biomedical complications will be associated with the development of mild neuropsychological dysfunction. The second study is cross-sectional and is designed to develop a model that explains the complex interactions among macrovascular complications, normal aging and its illnesses, chronic hyperglycemia, and neuropsychological processes. A major goal of the third study is to determine the etiology of memory disorders in diabetic adults. We have hypothesized that the memory disorders commonly seen in elderly Type 2 diabetic adults (but rarely reported in younger Type 1 diabetic adults) reflect an interaction between chronic hyperglycemia and aging.