Primary, secondary, tertiary, and quaternary treatment with troglitazone in type 2 diabetes mellitus in an outpatient clinical practice.

OBJECTIVE: To assess the value of troglitazone in various combinations of therapy with sulfonylureas, biguanides, and insulin, including triple oral agent therapy with and without insulin, in an outpatient clinical practice. METHODS: We compiled results in our first 207 patients with type 2 diabetes treated for 1 year with troglitazone. In eight study groups, troglitazone was added to the following prior regimens: (1) diet alone, (2) sulfonylurea, (3) metformin, (4) sulfonylurea and metformin, (5) insulin, (6) insulin and sulfonylurea, (7) insulin and metformin, and (8) insulin, sulfonylurea, and metformin. Glycosylated hemoglobin, fasting plasma glucose, hemoglobin, weight, and insulin dose were recorded every 3 months for 1 year and are reported. RESULTS: The glycosylated hemoglobin decreased in all study groups during the 1-year period. With the addition of troglitazone, it declined from 8.0% to 6.0% in the diet-only treatment group, from 8.9% to 7.3% in the sulfonylurea group, from 8.4% to 7.2% in the metformin group, and from 8.6% to 7.5% in the group treated with sulfonylurea and metformin. For the groups receiving insulin, glycosylated hemoglobin decreased in conjunction with a significant decline in insulin dose. The dose of insulin was reduced from a baseline of 62 to 41 U per patient in the insulin-only treatment group, from 36 to 12 U per patient in the group treated with insulin and sulfonylurea, and from 28 to 11 U per patient in the group treated with insulin and metformin. In the group treated with insulin, sulfonylurea, and metformin, the dose of insulin was decreased from 36 to 13 U. CONCLUSION: From our data in more than 200 patients with type 2 diabetes, who participated in a 1-year follow-up in an outpatient clinical practice, we found that troglitazone improved glycemic control in each study group and also decreased the insulin dose in the insulin-requiring patients. Troglitazone improves glycemic control as a primary, secondary, tertiary, or even quaternary therapy in patients with type 2 diabetes.

Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers.

OBJECTIVE: To assess the effect of a tissue-engineered human dermis (Dermagraft) in healing diabetic foot ulcers. RESEARCH DESIGN AND METHODS: This controlled prospective multicenter randomized single-blinded pilot study evaluated healing over a 12-week period in 50 patients with diabetic foot ulcers. These patients were randomized into four groups (three different dosage regimens of Dermagraft and one control group). All patients received identical care except for the use of Dermagraft tissue. Ulcer healing was assessed by percentage of wounds achieving complete or 50% closure, time to complete or 50% closure, and volume and area measurements. RESULTS: Ulcers treated with the highest dosage of Dermagraft, one piece applied weekly for 8 weeks (group A), healed significantly more often than those treated with conventional wound closure methods; 50% (6 of 12) of the Dermagraft-treated and 8% (1 of 13) of the control ulcers healed completely (P = 0.03). The percentage of wounds achieving 50% closure was also significantly higher (75 vs. 23%; P = 0.018), and the time to complete or 50% closure was faster (P = 0.056). The group A regimen was more effective than other treatment regimens. All three were better than the control, however, and a dose-response was observed. There were no safety concerns. After a mean of 14 months of follow-up (range 11-22 months), there were no recurrences in the Dermagraft-healed ulcers. CONCLUSIONS: Dermagraft was associated with more complete and rapid healing in diabetic foot ulcers. The recurrence data may indicate an improved quality of wound healing.

Bile acid metabolism in hereditary forms of hypertriglyceridemia: evidence for an increased synthesis rate in monogenic familial hypertriglyceridemia.

This study was undertaken to characterize bile acid metabolism in hereditary forms of hypertriglyceridemia. Ten hypertriglyceridemic patients (type IV phenotype) with familial combined hyperlipidemia and 7 patients with monogenic familial hypertriglyceridemia (FHTG) were compared with 18 healthy controls; all subjects were males. Pool size, synthesis rate, and fractional catabolic rate of cholic and chenodeoxycholic acids were determined with an isotope dilution technique. Patients with FHTG had synthesis rates of cholic acid, chenodeoxycholic acid, and total bile acids above those seen in normal controls (P less than 0.001); also the fractional catabolic rates of both bile acids were increased (P less than 0.001). In contrast, bile acid kinetic parameters were--with one exception--within normal limits in patients with familial combined hyperlipidemia. The abnormality of bile acid metabolism could also be identified in a normolipidemic individual presumed to carry the gene for FHTG. The postprandial rise of serum bile acids was blunted in FHTG, indicating that the intestinal uptake of bile acids may be deficient in this condition. We conclude that FHTG, but not familial combined hyperlipidemia, is frequently associated with a defective regulation of bile acid synthesis, resulting in abnormally high production rate of bile acids. It is hypothesized that this abnormality is important for the subsequent development of hypertriglyceridemia.

Prolactinomas as part of the multiple endocrine neoplastic syndrome type 1.

The pituitary tumors seen in the multiple endocrine neoplastic syndrome type 1 have generally been considered "nonfunctional." Fewer than 40 persons with hyperprolactinemia as part of the syndrome have been described. A family with the largest number of subjects (six) with prolactinomas in one generation reported to date is described. The variable aggressiveness of this disease, the difficulty in treatment because of multiple prolactinomas or hyperplasia or both, and a case of tumor shrinkage with bromocriptine therapy are also demonstrated in this unique family.

Insulin responses to glucose in non-insulin-dependent diabetic subjects with and without the chlorpropamide-alcohol flush: effect of salicylate and naloxone.

We examined the role of endogenous opiates and/or prostaglandins on the abnormal insulin secretion characteristic of some non-insulin-dependent diabetic subjects. A group of chlorpropamide-alcohol flush positive (CPAF+) and a group of flush negative (CPAF-) non-insulin-dependent subjects were compared as to their pancreatic beta-cell responses to intravenous glucose tolerance tests before and after sodium salicylate infusion, and before and after naloxone infusion. There was no difference in mean insulin secretion (either first or second phase) between CPAF+ versus CPAF- groups. Both groups increased their insulin secretion with salicylate infusion, and both had a small decrease with naloxone infusion. There was no correlation between chlorpropamide-alcohol flushing and beta-cell response to glucose.