Elias S. Siraj

EffECT Of SPIRONOlACTONE ThERAPy ON AlbumINuRIA IN PATIENTS WITh TyPE 2 DIAbETES TREATED WITh ANgIOTENSIN-CONVERTINg ENzymE INhIbITORS

OBJECTIVE To investigate whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors further decreases albuminuria in patients with type 2 diabetes mellitus (DM). METHODS We conducted a prospective open-label trial in patients recruited at the Cleveland Clinic between February 2004 and November 2006. Patients with type 2 DM were eligible if they were older than 18 years of age, had been treated with any ACE inhibitor for longer than 1 month, and had a random urinary albumin to creatinine ratio (ACR) greater than 100 mg/g within 1 month of study entry. Based on screening ACR, patients were assigned to a microalbuminuria group (ACR 100-300 mg/g) or a macroalbuminuria group (ACR >300 mg/g). Patients were followed up for 12 weeks, with 4 clinic visits, 4 weeks apart. At visit 2, spironolactone, 25 mg once daily, was initiated and continued for 4 weeks. At visit 3, spironolactone was discontinued. Clinical information was obtained at each visit as were serum chemistries and 24-hour urinary albumin excretion. RESULTS Twenty-four patients with type 2 DM and albuminuria completed the study. Eleven patients had microalbuminuria and 13 had macroalbuminuria. Following treatment with spironolactone, urinary albumin excretion dropped from a mean +/- SD of 404.6 +/- 60.9 mg/d to 302.7 +/- 52.7 mg/d (25.7% decrease, P<.001). In the microalbuminuria and macroalbuminuria groups, the urinary albumin excretion dropped 27.2% (P = .05) and 24.3% (P = .02), respectively. Despite a significant decrease in systolic blood pressure between visits 2 and 3 (141.2 +/- 3.5 to 132.5 +/- 3.6 mm Hg; P = .002), this change did not correlate to the change in albuminuria (r(2) = 0.02; P = .23). There were no withdrawals due to hyperkalemia. CONCLUSION Spironolactone is effective in further decreasing albuminuria in patients with type 2 DM who are already treated with ACE inhibitors.

Successful treatment of sulfonylurea-induced prolonged hypoglycemia with use of octreotide

OBJECTIVE To report the successful use of octreotide in the management of prolonged hypoglycemia attributable to therapeutic doses of sulfonylureas. METHODS We present a case series of 6 patients with sulfonylurea-induced hypoglycemia, along with pertinent serial laboratory data and review of the course of management. RESULTS Most of our 6 study patients had diabetes mellitus, which had been managed with sulfonylurea therapy. In the context of renal failure or heart failure (or both), severe, prolonged hypoglycemia developed. Intermittent intravenous administration of 50% dextrose did not result in a sustained and adequate response. Continuous intravenous administration of dextrose-containing solutions was contraindicated because of fluid overload as a result of congestive heart failure or renal failure. Administration of octreotide, 50 microg subcutaneously every 8 hours, resulted in a prompt and sustained resolution of the hypoglycemia. In 3 of the 6 study subjects, measurements of insulin and C-peptide levels both before and after treatment confirmed the efficacy of the octreotide therapy. CONCLUSION Our cases demonstrate that octreotide proves to be an effective treatment intervention for prolonged hypoglycemia caused by therapeutic doses of sulfonylureas. This is the first major report of the safe and effective use of octreotide in the management of sulfonylurea-induced hypoglycemia outside the emergency department setting.

A Simple Screening Method for Individuals at Risk of Developing Type 1 Diabetes: Measurement of Islet Cell Autoantibodies (GADA, IA-2A, and IAA) on Dried Capillary Blood Spots Collected on Filter Paper

There is limited information regarding the use of dried capillary blood spots collected on a filter paper (FP) to test for islet cell antibodies. The aim of this study was to validate the use of dried capillary blood spots collected on a FP for the analysis of islet cell antibodies. FP eluates were tested using both single and combined assay for antibodies to glutamic acid decarboxylase (GADA) and/or to the protein tyrosine phosphatase like IA-2 (IA-2A), and a single assay for antibodies to insulin (IAA). The results were compared with those of serum assays. Ninety-one subjects were studied. Forty had Type 1 diabetes mellitus (T1DM) and 51 were first-degree relatives (FDR) of patients with T1DM. The GADA and IA-2A were measured by radio-binding assays, which utilize 35S-labeled GAD65 and IA-2. IAA was measured by a microtiter plate assay using 125I-labeled insulin. Twenty-six of those with T1DM (65%) and 5 of the FDRs (10%) had at least 1 positive test on the single serum assays. The FP combi-assay for GADA and IA-2A had 97.8% concordance rate when compared with serum single assays for GADA and IA-2A. The concordance rate for individual assays were 96.7% for GADA, and 100% for both IA-2A and IAA There was significant correlation of the antibody levels between FP and serum specimen for all 3 antibodies. We conclude that antibody screening performed using dried capillary blood spots collected on a FP correlates well with serum assays, and provides an easy alternative for population screening.

METASTATIC MALIGNANT INSULINOMA IN A PATIENT WITH TYPE 2 DIABETES MELLITUS: CASE PRESENTATION AND LITERATURE REVIEW

OBJECTIVE To describe the occurrence of metastatic malignant insulinoma in a patient with preexisting type 2 diabetes mellitus. METHODS We present a detailed case report, with clinical, biochemical, and imaging findings, and summarize the data from 21 similar cases in the literature. RESULTS The occurrence of malignant insulinoma in a patient with preexisting diabetes is very rare and thus can be a diagnostic challenge. In our patient with type 2 diabetes, endogenous hyperinsulinism was confirmed by demonstrating elevated insulin and C-peptide levels during hypoglycemic episodes in the absence of sulfonylurea on a blood screen. Abdominal computed tomographic scan and magnetic resonance imaging revealed a pancreatic mass as well as metastatic lesions in the liver. The pancreatic mass was removed and confirmed to be a malignant insulinoma. This procedure was followed by disappearance of the hypoglycemic episodes as well as the diabetes for a few months. On follow-up, however, more metastatic lesions appeared in conjunction with a protracted course of hypoglycemia that necessitated treatment with antihypoglycemic agents and, 3 years after the initial surgical intervention, culminated in the death of the patient. CONCLUSION Our patient is one of the few subjects known to have a malignant insulinoma in conjunction with preexisting diabetes. A high degree of suspicion for the presence of an insulinoma should be maintained when unexplained hypoglycemic episodes occur in a patient with previously stable diabetes.