Concurrent diagnosis of acromegaly and diabetic ketoacidosis.

OBJECTIVE: To report the occurrence of diabetic ketoacidosis (DKA) in a patient with acromegaly. METHODS: A case report with clinical and laboratory details is presented, and the few other cases of DKA and acromegaly from the literature are discussed. RESULTS: A 37-year-old man requested a consultation because of nausea, vomiting, polydipsia, polyuria, and weight loss. Physical examination revealed findings suggestive of acromegaly, including coarse facial features and enlargement of his hands and feet. Laboratory studies confirmed the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the presence of a pituitary adenoma, which was subsequently removed surgically. Although the DKA had been managed with insulin therapy, 2 weeks postoperatively the insulin dose was tapered and then discontinued because of hypoglycemia. Follow-up showed normalization of growth hormone levels and plasma glucose levels. Only three other cases of DKA associated with acromegaly were found in the medical literature. CONCLUSION: Although DKA is rarely diagnosed in conjunction with acromegaly, this unusual association was confirmed in the current patient.

Diabetic ketoacidosis in association with acanthosis nigricans.

OBJECTIVE: To report the occurrence of diabetic ketoacidosis in three patients with acanthosis nigricans. METHODS: Case reports with clinical and laboratory data are presented, and the syndrome of acanthosis nigricans is discussed. RESULTS: Three obese male patients--two American Indians and one Polynesian man--sought medical attention because of symptoms of diabetic ketoacidosis and were noted to have acanthosis nigricans. No factor was identified that could have precipitated the diabetic ketoacidosis, which was resolved by treatment with insulin. CONCLUSIONS: The unexpected association of diabetic ketoacidosis and acanthosis nigricans is documented in these three cases. The hyperinsulinemia associated with acanthosis nigricans results from insulin resistance, and when insulin resistance occurs in combination with impaired insulin secretion, diabetic ketoacidosis can result.

Acute metabolic response to high-carbohydrate, high-starch meals compared with moderate-carbohydrate, low-starch meals in subjects with type 2 diabetes.

OBJECTIVE: The monosaccharides resulting from the digestion of ingested carbohydrates are glucose, fructose, and galactose. Of these three monosaccharides, only ingested glucose resulted in a large increase in the plasma glucose concentration. Fructose (Metabolism 41:510-517, 1992) and galactose (Metabolism 42:1560-1567, 1993) had only a minor effect. Therefore, we were interested in determining whether we could design a mixed meal, using foods of known monosaccharide, disaccharide, and starch composition, the ingestion of which would result in only a small rise in plasma glucose concentration. RESEARCH DESIGN AND METHODS: The experimental meal was composed of very little readily digestible starch but rather large amounts of fruits and vegetables. It contained 43% carbohydrate, 22% protein, and 34% fat. The results were compared with a second type of meal that contained 55% carbohydrate, 15% protein, and 30% fat, with an emphasis on complex carbohydrates (starch). It also was compared with a third meal that contained 40% carbohydrate, 20% protein, and 40% fat, typical of that consumed by the average American. The test meals were ingested in random order by people with type 2 diabetes who were not treated with oral hypoglycemic agents or insulin. Each subject ingested each type of meal. The same identical meal was ingested at 0800, 1200, and 1700. RESULTS: The integrated 24-h plasma glucose area response was statistically significantly smaller (P < 0.05) after ingestion of the low-starch meals compared with the high-starch, high-carbohydrate meals or the typical American meals. The 24-h integrated serum insulin area response also was statistically significantly less (P < 0.05) after ingestion of the low-starch meals compared with the high-starch meals or the typical American meals. The serum triglyceride area response was similar after ingestion of all three test diets. CONCLUSIONS: A diet in which fruits, nonstarch vegetables, and dairy products are emphasized may be useful for people with type 2 diabetes.

Disseminated coccidioidomycosis associated with hypercalcemia.

This article describes a patient in whom disseminated infection with coccidioidomycosis was associated with hypercalcemia. The patient had a low level of 1,25-dihydroxyvitamin D and a suppressed parathyroid hormone value, an indication that the hypercalcemia was not mediated by vitamin D or parathyroid hormone. The episode resolved readily with administration of pamidronate, an outcome suggesting that this is effective treatment of hypercalcemia of this origin. On follow-up of the patient while he was receiving antifungal therapy for Coccidioides immitis, calcium values remained normal.

Unusual presentations of hypothyroidism.

Hypothyroidism is a commonly diagnosed endocrine disorder. Typical signs and symptoms of hypothyroidism include lethargy, cold intolerance, hoarseness, dry skin, constipation, delayed relaxation phase of deep tendon reflexes, and bradycardia. Hypothyroidism, presenting with such classic manifestations, usually is readily recognized and, therefore, easy to diagnose. Occasionally patients have less commonly emphasized symptoms, making the diagnosis less apparent. Such atypical presentations may suggest other diseases as the primary problem and, therefore, the initial focus of attention is on a diagnosis other than hypothyroidism. We have observed patients with hypothyroidism with rare manifestations. The diagnosis of primary hypothyroidism was established in all patients by thyroid function tests, and initiation of thyroid hormone therapy resulted in significant improvement of the presenting symptom. We considered it instructive to report about these patients because it shows the need to be aware of the unusual presentations of hypothyroidism and to consider hypothyroidism when confronted with atypical clinical manifestations.

Recombinant human granulocyte colony-stimulating factor in treatment of methimazole-induced agranulocytosis.

OBJECTIVE: To describe a patient with methimazole-induced agranulocytosis who was treated with recombinant human granulocyte colony-stimulating factor (G-CSF). METHODS: A case report is presented, in which the clinical and laboratory findings are detailed and the response to treatment is discussed. Pertinent reports from the literature are reviewed. RESULTS: In a 24-year-old woman with Graves' disease who was treated with methimazole, a fever and sore throat developed; bone marrow examination revealed absence of granulocytes. After discontinuation of methimazole therapy, treatment with G-CSF was implemented in an attempt to hasten the reappearance of the granulocytes. The patient's granulocyte count reached 0.5 10(9)/L on the 9th hospital day and was more than 1.5 10(9)/L on the 10th day. Because the recovery time for thionamide-induced agranulocytosis typically ranges from 1 to 2 weeks and sometimes is even longer, G-CSF may have been beneficial in accelerating the return of the granulocytes. CONCLUSION: Only a small number of patients with thionamide-induced agranulocytosis have had G-CSF treatment, and most outcomes have generally supported a beneficial effect. More experience is needed with the use of G-CSF in such circumstances. Nevertheless, its use seems to be a reasonable therapeutic option for consideration in patients with thionamide-induced agranulocytosis.

The occurrence of diabetic ketoacidosis in non-insulin-dependent diabetes and newly diagnosed diabetic adults.

PURPOSE: To examine the occurrence of diabetic ketoacidosis (DKA) in adults without a prior history of type I diabetes. PATIENTS AND METHODS: A retrospective review was conducted of medical records of adults presenting with DKA between 1987 and 1993. The medical record was reviewed to classify patients as type I, type II, or newly diagnosed diabetics and to determine the status of diabetic treatment following the episode of DKA in those patients without prior history of type I diabetes. RESULTS: Two hundred twenty-six patients were included in the study; 106 (47%) were classified as type I and 58 (26%) as type II from data available in the medical record, and 62 (27%) had DKA as the initial manifestation of the disease. Nineteen percent of the patients in whom diabetes was a new diagnosis and 52% of the patients who had a prior history of NIDDM were > or = 40 years old. Of patients with follow-up of at least 12 months, about 24% of the newly diagnosed and 8% of those with a history of NIDDM were not taking insulin. CONCLUSION: DKA occurs in patients with type II diabetes. Older patients may present with clinically apparent type I diabetes. Some adults who present with DKA do not remain insulin dependent.

A pilot study of urine iodine excretion in a selected cohort in phoenix.

A pilot study of twenty-four hour urine iodine excretion was carried out in 34 adults who were employees (or their spouses) of Maricopa Medical Center and residents of the Phoenix area. Based on previous estimations, our expectation was that urine iodine excretion values should be high. The mean value was 219 +/- 25 microg/day in the first collection and 229 +/- 23 microg/day when the collection was repeated 4 months later. The results support an adequate amount of iodine in the diet for the group. However, they indicate an iodine intake lower than what previously published studies had estimated for this area. It is not clear whether these results reflect a regional or national trend of decreased dietary iodine intake or changes in dietary iodine intake limited to the cohort studied. These data indicate a need for further study to clarify this finding in view of possible clinical implications resulting from changes in iodine intake.

Hepatotoxicity from propylthiouracil.

Propylthiouracil is a drug used commonly to treat hyperthyroidism. Among its side effects, hepatotoxicity is one of the rarest but one of the most serious. This complication may be due to an immune mechanism. However, particular risk factors associated with the development of hepatotoxicity are not known, and its occurrence is unpredictable. I report a case of acute hepatitis developing during propylthiouracil therapy for Graves' disease and review the literature related to this problem.

Seasonal variation in the diagnosis of Graves' disease.

OBJECTIVE: Heat intolerance is a well known symptom of Graves' disease. Therefore, it is possible that increased ambient temperature could influence the recognition of Graves' disease by unmasking or enhancing the symptom of heat intolerance. Our aim was to determine if there is a seasonal variation in the diagnosis of Graves' disease. DESIGN: A retrospective study. SETTING: A county hospital and clinic. PATIENTS: Two hundred and seven patients with Graves' disease diagnosed from 1985 to 1992. RESULTS: A high correlation was found between the temperature and the number of cases of Graves' disease diagnosed. A larger proportion of patients (68%) was diagnosed during the warmer half of the year, May-October, than during the cooler half. The peak incidence of the diagnosis occurred in May, when 17.4% of the patients were diagnosed. Although the peak average monthly temperature occurs in July, the month of May corresponds to the time of the year when the temperature is making its largest positive change in the month-to-month variation. CONCLUSIONS: Seasonal variations in the temperature can affect the incidence of the diagnosis of Graves' disease. The diagnosis is more common during the months of higher temperature.

Diabetic ketoacidosis associated with pulmonary coccidioidomycosis.

We describe three patients who developed diabetic ketoacidosis in association with pulmonary coccidioidomycosis and review the literature concerning the influence of diabetes on coccidioidomycosis. Our cases demonstrate that coccidioidomycosis is an infection that can be associated with diabetic ketoacidosis and that should be considered in the differential diagnosis of pneumonia in patients who live in a region in which Coccidioides immitis is endemic.

Plasma glucose and insulin responses to bananas of varying ripeness in persons with noninsulin-dependent diabetes mellitus.

With progressive ripeness there is a decrease in starch and an increase in free sugar content of bananas. The starch also is considered to be poorly digestible. Therefore, we decided to study plasma glucose, serum insulin, C-peptide, and plasma glucagon responses to bananas with increasing degrees of ripeness. Seven male subjects with untreated noninsulin-dependent diabetes mellitus ingested 50 g carbohydrate as bananas of stage 4 (more yellow than green), 5 (yellow with green tip), 6 (all yellow), and 7 (yellow flecked with brown) ripeness. They also received 50 glucose on two occasions for comparative purposes. On a separate occasion water only was given as a control. The area responses were quantified by determining incremental areas using the water control as baseline. The mean glucose area following the 50 g glucose meals was 15.1 +/- 1.9 mM.h. After the ingestion of bananas of 4, 5, 6 and 7 ripeness the glucose area response was 42, 41, 51 and 48% of that after glucose ingestion, respectively. The insulin area response following glucose meals was 888 pM.h. Responses to 4, 5, 6 and 7 bananas were 85, 70, 61, 85%, respectively, of that following glucose ingestion. C-peptide data were similar to the insulin data. The glucagon area response was negative after glucose ingestion but was positive following banana ingestion. In summary, the glucose, insulin, C-peptide, and glucagon area responses varied little with ripeness of the bananas.

Effect of added fat on plasma glucose and insulin response to ingested potato in individuals with NIDDM.

OBJECTIVE: In normal subjects, ingestion of butter with potato resulted in considerably lower blood glucose levels but similar or higher insulin concentrations compared with those observed in the same subjects after potato ingestion alone. We determined whether butter ingested with potato would result in a greater stimulation in insulin secretion than ingestion of potato alone in subjects with NIDDM. RESEARCH DESIGN AND METHODS: Seven male subjects with untreated NIDDM ingested 50 g CHO alone or 50 g CHO with 5, 15, 30, or 50 g fat as a breakfast meal. Fat was ingested in the form of butter, and CHO was given in the form of potato. Subjects received 50 g glucose on two separate occasions for comparative purposes. The subjects also were given only water and were studied over the same time period (water control). Plasma glucose, glucagon, alpha-amino nitrogen, nonesterified fatty acids, serum insulin, C-peptide, and triglyceride concentrations were determined over 5 h. The integrated area responses were quantified over the 5-h period using the water control as a baseline. RESULTS: The mean plasma glucose area response after ingestion of potato with or without the various amounts of butter were all similar and were 82% of that observed after ingestion of 50 g glucose. The mean insulin area response to potato alone was 532 pmol.h.L-1. The mean insulin area responses to potato plus 5,15,30, and 50 g of fat meals were 660,774,750, and 756 pmol.h.L-1, respectively. Thus, the mean insulin areas were all greater than for ingestion of potato alone, and a maximal response was observed with addition of 15 g fat (1.4-fold). The C-peptide data did not confirm an increase in insulin secretion. Overall the area responses after ingestion of meals containing fat were not different from the response to potato ingestion alone, although the responses were erratic. The glucagon area response was positive after ingestion of all fat containing meals except for that containing only 5 g fat, and there was a dose-response relationship. The plasma alpha-amino nitrogen and nonesterified fatty acid area responses were negative after potato ingestion and were not significantly different when fat was added. The serum triglyceride concentration increase was greater after the ingestion of butter with the potato as expected. CONCLUSIONS: In contrast to the results in normal subjects after ingestion of butter with potato, the glucose response was not smaller in subjects with NIDDM. The insulin response was greater. The insulin area response data indicated the presence of a dose-response relationship. Whether similar responses will be observed with other dietary fat and CHO sources remains to be determined.

The effect of fat and carbohydrate on plasma glucose, insulin, C-peptide, and triglycerides in normal male subjects.

Ten normal subjects were given 50 g starch, or 50 g starch + 50 g fat as a breakfast meal. The starch was given in the form of potato; the fat was given in the form of butter. The meals were ingested at 8 a.m. Plasma glucose, insulin, C-peptide, and triglyceride concentrations were measured at various time points for 4 hours after each meal. The net 4-hour postprandial area responses to the ingested meals were determined using the trapezoid rule, with the fasting glucose concentration, measured at the same time points for 4 hours as a baseline. The glucose area response was 2.2 mmol hour/l following the potato meal. This was significantly reduced following ingestion of the meal containing fat (1.3 mmol hour/l) (p < 0.01). The insulin area response was slightly greater following the meal containing fat (459 pmol hour/l) compared to potato alone (423 pmol hour/l) (p < 0.01). The C-peptide area response following the meal containing fat was 0.80 pmol hour/ml, clearly greater than following potato alone (0.58 pmol hour/ml) (p < 0.01). The triglyceride area response also was much greater following the meal containing fat compared to potato alone (0.74 and 0.08 mmol hour/l, respectively). The mechanism of the attenuated glucose response to carbohydrate ingestion with a fat-containing meal is unknown. It may be due to the release of an enteric hormone that increases glucose disposal, either directly or indirectly, through insulin.

Comparative characterization of human and rat liver glycogen synthase.

Glycogen synthase from human liver was studied, and its properties were compared with those of rat liver glycogen synthase. The rat and human liver glycogen synthases were similar in their pH profile, in their kinetic constants for the substrate UDP-glucose and the activator glucose 6-phosphate, and in their elution profiles from Q-Sepharose. The apparent molecular weight of the human synthase subunit was 80,000-85,000 by gel electrophoresis, which is similar to that of the rat enzyme. In addition, antibodies to rat liver glycogen synthase recognized human liver glycogen synthase, indicating that the enzymes of these two species share antigenic determinants. However, there were significant differences between the two enzymes. In particular, the total activity of the human enzyme was higher than that of the rat. The human enzyme, purified to near homogeneity, had a specific activity of 40 U/mg protein compared with 20 U/mg protein for the rat enzyme. The active forms of the rat enzyme had greater thermal stability than those of the human enzyme, but the human enzyme was more stable on storage in various buffers. Last, amino acid analysis indicated differences between the enzymes of the two species. Since glycogen synthase is an important enzyme in liver glycogen synthesis, the characterization of this enzyme in the human will help provide insight regarding human liver glycogen synthesis.

Metabolic response to glucose ingested with various amounts of protein.

Seven healthy, normal-weight subjects were fed breakfasts of 50 g protein, 50 g glucose, and 10, 30, or 50 g protein plus 50 g glucose in random sequence. Plasma glucose, insulin, C peptide, glucagon, nonesterified fatty acids, and alpha-amino nitrogen were then measured from samples obtained over 4 h. The postmeal net area of each response curve was calculated. Ingestion of 50 g protein alone did not change the serum glucose concentration. The various amounts of protein ingested with 50 g glucose also did not alter the serum glucose response compared with that observed with 50 g glucose alone. Ingestion of the various amounts of protein also did not result in a further increase in insulin concentration when ingested with glucose, except with the 50-g-protein dose. This increase was modest. Ingestion of glucose resulted in a decrease in alpha-amino nitrogen and glucagon concentrations whereas ingestion of protein increased them as expected. Additions of progressively larger amounts of protein to the glucose meal resulted in a progressive increase in the alpha-amino-nitrogen- and glucagon-area responses. The relationship was curvilinear for both the alpha-amino-nitrogen response and the glucagon response. The null point, that is, the protein dose ingested with 50 g glucose at which there would be no change in area response, was estimated to be 9 g protein for alpha-amino nitrogen and 5 g protein for glucagon.

Effects of dose of ingested glucose on plasma metabolite and hormone responses in type II diabetic subjects.

Ten untreated type II (non-insulin-dependent) diabetic subjects were given 15, 25, 35, and 50 g glucose orally. Plasma glucose, insulin, C-peptide, glucagon, urea nitrogen, alpha-amino acid nitrogen, and lactate concentrations were measured, and net 5-h postprandial areas were calculated. The net glucose-area response to the ingested glucose dose (with the 0-time value as a constant baseline) was best described by a second-order polynomial equation, whereas insulin-area response was best described by a third-order equation. In a separate study, 5 untreated type II diabetic subjects were given only water, and the same metabolites and hormones were measured. Data from this study indicated that the baseline was not constant during the 5 h of study but decreased progressively. The net glucose-area and insulin-area responses to ingested glucose dose (with the decreasing baseline) were then best described by third-order equations. Glucagon, alpha-amino acid nitrogen, and lactate concentrations were exquisitely sensitive to a rise in glucose and insulin concentrations. These were all decreased with the lowest concentration of glucose used. At this dose of glucose, the increase in insulin was only 15 microU/ml.