Alan L. Graber

Clinical Use of Diazoxide and Mechanism for Its Hyperglycemic Effects

The mechanism of diazoxide hyperglycemia in man has been studied by measurement of serum glucose, immunoreactive insulin, and plasma free fatty acids. In a patient with islet cell carcinoma, in normal subjects, and in diabetic patients, diazoxide hyperglycemia was accompanied by a decrease in serum immunoreactive insulin, an increase in plasma free fatty acids, tachycardia, and a widened pulse pressure. The similarity of these effects to those produced by epinephrine has suggested that at least some of the effects of diazoxide may be mediated by endogenous sympathetic stimulation. Diazoxide has been used successfully to control hypoglycemia in a patient with islet cell carcinoma for twenty months.

Dropout and relapse during diabetes care.

OBJECTIVE To determine factors associated with dropout and relapse during chronic diabetes care. RESEARCH DESIGN AND METHODS Private practice outpatient treatment-education program for adult diabetes was surveyed. Retrospective analysis was done, involving 422 patients for up to 3 yr. RESULTS Of the patients in the study, 12% dropped out after the initial visit, and 33% of the residual cohort dropped out during each subsequent 6-mo period. Factors associated with dropout included distance from home to clinic > 100 miles, lack of insulin treatment, and cigarette smoking. In patients who remained in follow-up, a significant decrease in HbA1C occurred during the first 6 mo, but 40% of the patients relapsed between 6 and 12 mo. Frequency of relapse declined as time passed. Relapse was more frequent in women. CONCLUSIONS Dropout from treatment and relapse after temporary improvement account for a substantial amount of uncontrolled diabetes, and overcoming the obstacles of dropout and relapse has potential for significant improvement in diabetes care.

Evaluation of diabetes patient-education programs.

Patient education is generally regarded as an essential component of the clinical management of diabetes. However, analysis of the role of patient education in diabetes control has been limited. Formal patient teaching programs at several medical centers range in operation from merely providing knowledge about diabetes to integrating patient education into the chronic health care system. Improvements in knowledge about diabetes have been demonstrated with patients who have been given questionnaires before and after instruction, but changes in diabetes control and other clinical parameters have not necessarily followed. In those cases in which patient education has been a part of a comprehensive improvement in the entire clinical management of diabetes, significant decreases in rates of hospitalization and acute complications have occurred. Guidelines for future evaluations are discussed.

CLINICAL USE OF DIAZOXIDE AND STUDIES OF THE MECHANISM OF ITS HYPERGLYCEMIC EFFECTS IN MAN

Diazoxide, a nondiuretic benzothiadiazine compound with potent hyperglycemic effects in animals and man, has been used successfully for 31 months (as of January, 1967) to control hypoglycemia in a young woman with islet cell carcinoma. Studies performed in this patient have indicated that the hyperglycemic effect of diazoxide is associated with a decrease in serum immunoreactive insulin; additional studies have shown that similar effects occur in normal and diabetic subjects.

Syndrome of lipodystrophy, hyperlipidemia, insulin resistance, and diabetes in treated patients with human immunodeficiency virus infection.

OBJECTIVE To describe the syndrome of lipodystrophy, hyperlipidemia, insulin resistance, and diabetes in patients with human immunodeficiency virus (HIV) infection treated with protease inhibitor drugs. METHODS This is a case series of patients referred from an infectious disease clinic to a diabetes-endocrinology clinic in an academic medical center because of severe metabolic problems that occurred during the course of otherwise-successful treatment of HIV infection. The clinical course, abnormalities on physical examination, laboratory data, and complications are described and analyzed. The pathogenesis of the syndrome is discussed and compared with that of type 2 diabetes, lipoatrophic diabetes, and mouse models of lipodystrophy. RESULTS In six male patients receiving antiretroviral therapy for HIV infection, a syndrome of lipoatrophy of the face, legs, and buttocks, hyperlipidemia (predominantly hypertriglyceridemia), and type 2 diabetes mellitus was noted. Two patients had pronounced abdominal obesity, in contrast to their thin extremities. Five of the six patients were receiving protease inhibitor drugs, which have been thought to contribute to metabolic abnormalities. In two patients, ischemic heart disease had developed. CONCLUSION Protease inhibitors frequently cause insulin resistance and lipoatrophy in subcutaneous adipose tissue. These abnormalities are associated with visceral adiposity, hyperlipidemia, diabetes, and cardiovascular consequences and represent an important and unsolved problem in the treatment of HIV-infected patients.

Serum immunoreactive insulin response during prolonged glucose infusions in nondiabetic and diabetic humans.

Prolonged intravenous glucose infusions were employed to study pancreatic islet cell reserve, measured by responses in serum immunoreactive insulin levels. A continuous intravenous glucose load (6 gm./kg./24 hrs.) was administered for five to seven days to four nondiabetic subjects and five maturity-onset diabetic patients. The nondiabetics assimilated all the glucose, but the diabetics developed marked hyperglycemia and glucosuria. Immunoreactive insulin levels were similar in the two groups, and insulin response to eating breakfast daily during the infusions was at least as high in the diabetics as in the nondiabetics. During these infusions, there was no evidence that the diabetic patients differed from the nondiabetic controls by showing progressive decreases in serum immunoreactive insulin responses.

HOSPITALIZATION OF PATIENTS WITH DIABETES

To determine annual hospitalization rates for patients with diabetes mellitus, we retrospectively analyzed the frequency of hospitalization among 905 patients with diabetes receiving primary care in a private practice outpatient program during a 20-month period (1,508 patient-years). We assessed the annual hospitalization rates stratified by diabetes clinical severity index, type of diabetes, type of treatment, age, sex, and mean glycosylated hemoglobin. The all-cause annual hospitalization rate was 211 per 1,000 patients (95% confidence interval, 184 to 238). Hospitalization rates were strongly correlated with measures of clinical severity; hospitalization rates did not vary significantly with type of diabetes, age, or sex. Among patients with type II diabetes, rates were higher in the group treated with insulin. A trend was noted for hospitalization rates to increase with mean glycosylated hemoglobin (not statistically significant in this sample). Overall, 14% of hospitalizations were for metabolic reasons, 45% were related to clinical complications of diabetes, and 41% were unrelated to the presence of diabetes. In analysis of hospitalization rates and therefore health-care expenditures for patients with diabetes, the characteristics of the patient population--and especially measures of clinical severity--must be considered. Interventions to reduce hospitalization can be targeted at high-risk groups.

Effect of prolonged glucose infusion on serum protein-bound glucosamine and protein-bound hexose in non-diabetic and diabetic patients.

Summary Serum protein-bound gluco-samine and protein-bound hexose were measured during prolonged glucose infusions in non-diabetic and diabetic subjects. Negligible changes in either of these substances occurred in either group.