Stephen E Dippe

Hyperinsulinemia and hypoinsulinemai. Insulin responses to oral carbohydrate over a wide spectrum of glucose tolerance.

Oral glucose tolerance tests using a 75 gm. carbohydrate load were performed on 396 Pirna Indians. Subjects were divided into groups on the basis of two-hour plasma glucose levels and the patterns of insulin response examined. Two-hour insulin levels were highest in the group with two-hour plasma glucose levels between 140–169 mg./100 ml. and then fell progressively until levels above 400 mg./100 ml. were reached. Half and one-hour insulin levels showed little change in the groups with two-hour glucose levels up to 170 mg./100 ml., but at higher glucose levels these insulin levels also progressively diminished. Fasting insulin levels were relatively unchanged over the entire range of glucose tolerance. Obesity was the most important factor influencing the fasting insulin levels. Glucose level was the major determinant of post-load insulin responses, but these were also significantly influenced by obesity. No effect of age or sex on insulin levels was demonstrated. Comparison with other published data indicates that different interpretations of insulin response in subjects with “mild diabetes” have resulted from comparisons of groups with different degrees of glucose intolerance.

A clinical and histologic study of diabetic nephropathy in the Pima Indians.

The relationship of renal disease to carbohydrate tolerance was examined in the Pima, who are American Indians with a high prevalence of diabetes mellitus. Glucose tolerance, serum creatinine level and urine protein concentration were measured in 1,716 subjects aged fifteen and over, of whom 404 were diabetic. Histologic information was obtained by reviewing autopsy material from forty-three diabetics and sixty-two nondiabetics. Over 22 per cent of the diabetics and less than 7 per cent of the nondiabetics had proteinuria (p < 0.001). Severe proteinuria aid elevated serum creatinine levels were, respectively, fifteen and nine times more common in the diabetics (p < 0.001). Both the frequency and severity of renal disease increased with duration of diabetes in subjects who were under age sixty-five when examined or when the disease was diagnosed. Above age sixty-five the prevalence of proteinuria was high in all duration groups. At autopsy, 65 per cent of the diabetics had diffuse glomerulosclerosis. Nodular glomerulosclerosis was found in 56 per cent of the diabetics and in none of the nondiabetics. Arteriolar lesions were also significantly more common in the diabetics. Pyelonephritis was found in 16 per cent of the diabetics and 5 per cent of the nondiabetics; other forms of renal disease were rare in both groups. Diabetic nephropathy, similar in its clinical and histologic characteristics to that described in other populations, is the predominant form of kidney disease in the Pima Indians, making this population ideal for study of the development and course of diabetic renal disease.

Are Abnormalities in Insulin Secretion Responsible for Reactive Hypoglycemia

Seventy patients with reactive hypoglycemia strictly defined by criteria which interpret the low blood glucose value in relationship to clinical and physiologic parameters, were studied to determine if abnormalities in insulin secretion could be demonstrated. These patients were separated into four groups: alimentary (N = 5), diabetic (N = 16), hormonal (N = 5), and idiopathic (N = 44). The findings in these patients were compared to normal control subjects and to weight- and disease-matched patient controls. All of the patients with hormonal and most patients with idiopathic reactive hypoglycemia (thirty-two of forty-four) demonstrated delayed insulin secretion regardless of the control group used for comparison. Diabetic reactive hypoglycemic patients exhibited delayed insulin secretion when compared to normal controls but not when compared to weight-matched diabetic controls. Excessive insulin secretion was consistently found only in the patients with the alimentary variety of reactive hypoglycemia. Using weight- and diseasematched control groups, no abnormalities in insulin secretion could be found to account for the hypoglycemia in the diabetic reactive hypoglycemic patients and some idiopathic reactive hypoglycemic (nine of forty-four) patients. These results help to explain the inconsistent findings of previous investigators and suggest that reactive hypoglycemia is a syndrome having multiple etiologies.

Effects of Diphenylhydantoin upon Glucose-induced Insulin Secretion in Three Patients with Insulinoma

Because diphenylhydantoin (DPH) has been shown to inhibit nontumorous insulin release, we evaluated its effects in patients with insulinoma. Three patients with surgically demonstrated insulinomas were tested with oral and intravenous glucose before and after DPH. In two of these patients, we compared the effects of DPH and diazoxide. Ingestion of DPH for several days did not alter fasting glucose or insulin. Poststimulatory insulin was appreciably reduced in only one patient during treatment with the drug. During diazoxide administration, this patient had increased fasting glucose and decreased fasting insulin, in addition to reduction of poststimulatory insulin. Combined DPH-diazoxide therapy in this patient did not produce greater effects than did diazoxide alone. Neither fasting ingulin or glucose nor poststimulatory insulin secretion were influencse by DPH or diazoxide in the second patient, or affected by DPH alone in the third. The accepted role of DPH in the treatment of insulinoma involves its ability to alter seizure threshold. It did not influence fasting hypoglycemia in our patients. Reduced insulin secretion after stimuli might reflect effects of DPH on responses of nontumorous endocrine pancreas.

Personality Disorder and Reactive Hypoglycemia: A Quantitative Study

Thirty-seven previously diagnosed reactive hypoglycemic patients (HP) were evaluatedand classified according to blood glucose nadir and plasma cortisol response to the nadir. We found eight definite, ten probable, and thirteen possible HP. Six patients were vaguely symptomatic without chemical evidence of hypoglycemia. Underlying etiology for the HP included nine diabetics, seven alimentary, thirteen idiopathic, one hypothyroid, and one with liver disease. The Minnesota Multiphasic Personality Inventory (MMPI) was given to all the patients and to twenty-one patients with various endocrine disorders without hypoglycemic symptoms. HP had mean scores two standard deviations above normal on hypochondriasis and hysteria scales with all other scales within normal limits. Definite, probable, and possible HP did not differ significantly from each other. HP differed significantly from mixed endocrine patients on the Hs and Hy scales (p < .001) and from vaguely symptomatic patients on the Hy scale (p < .05). The latter groups were normal on all scales. HP of varying etiology (diabetic, alimentary, or idiopathic) show the same MMPI pattern. Thispattern differs from that shown in previous MMPI studies of diabetic patients and patients with gastric surgery without hypoglycemia. Thus, a relationship between hypoglycemia, of whatever origin, and this specific personality pattern is suggested.