Claresa Levetan

Unrecognized Diabetes Among Hospitalized Patients

OBJECTIVE To evaluate the hospital care rendered to hyperglycemic individuals who did not have a diagnosis of diabetes before admission. RESEARCH DESIGN AND METHODS A total of 1,034 consecutively hospitalized adult patients at a 750-bed inner-city teaching hospital were evaluated. Patients with one or more plasma glucose values >200 mg/dl were identified by the laboratory data system on a daily basis. Patients without a diagnosis of diabetes at the time of admission were evaluated to determine if and how physicians addressed the hyperglycemia, whether a new diagnosis of diabetes was made during admission, and whether follow-up was planned to address the hyperglycemia. RESULTS After excluding patients who were admitted for a primary diagnosis of diabetes, 37.5% of all hyperglycemic medical patients and 33% of hyperglycemic surgical patients were without a diagnosis of diabetes at the time of admission. These patients had a mean peak glucose of 299 mg/dl, and 66% had two or more elevated values during their hospitalization. Fifty-four percent received insulin therapy, and 59% received bedside glucose monitoring, yet 66% of daily patient progress notes failed to comment on the presence of hyperglycemia or diabetes. Diabetes was documented in only three patients (7.3%) as a possible diagnosis in the daily progress notes. CONCLUSIONS Despite marked hyperglycemia, most medical records made no reference to the possibility of unrecognized diabetes. Given the average delay of a decade between the onset and diagnosis of type 2 diabetes, further evaluation of hyperglycemic hospitalized patients may present an important opportunity for earlier detection and the initiation of therapy.

Impact of endocrine and diabetes team consultation on hospital length of stay for patients with diabetes

PURPOSE To determine whether consultation by an individual endocrinologist or by a multidisciplinary diabetes team (endocrinologist, diabetes nurse educator, and registered dietitian) can impact length of hospital stay of patients with diabetes. PATIENTS AND METHODS Hospital stays of consecutive patients with a principal diagnosis of diabetes were compared. Forty-three patients were seen by an individual endocrine consultant and 27 were managed by the internist alone. Thirty-four patients were seen in consultation by the diabetes team. All consultations were performed at the request of the primary physician. There were no statistically significant differences among groups with respect to age, duration of diabetes, admitting diagnosis, glucose levels, or concomitant acute or chronic illness. RESULTS Average length of stay of diabetes-team patients was 3.6 +/- 1.7 days, 56% shorter than the value, 8.2 +/- 6.2 days, of patients in the no-consultation group (P < 0.0001), and 35% shorter than the value, 5.5 +/- 3.4 days, of patients who received a traditional individual endocrine consultation (P < 0.05). The length of stay correlated with time from admission to consultation (regression equation: y = 3.92 + [1.09 x time to consultation]; r = .55; P < 0.0001). The slope (1.09) indicates that each 1-day delay in consultation resulted in a 1-day increase in length of stay. CONCLUSIONS Length of stay was lowest in patients who received diabetes-team consultation. Three million Americans are hospitalized annually with diabetes at a cost of

Use of the Continuous Glucose Monitoring System to Guide Therapy in Patients With Insulin-Treated Diabetes: A Randomized Controlled Trial

65 billion. A team approach to their inpatient care may reduce their hospital stays, resulting in considerable health and economic benefits.

Hospital management of diabetes

OBJECTIVE To show improved glycemic control in patients with insulin-treated diabetes after adjustments to the diabetes management plan based on either continuous glucose monitoring using the Continuous Glucose Monitoring System (CGMS) or frequent self-monitoring of blood glucose (SMBG) using a home blood glucose meter. PATIENTS AND METHODS From January to September 2000, patients aged 19 to 76 years with insulin-treated diabetes were assigned to insulin therapy adjustments based on either CGMS or SMBG values. At the end of the study, patients in both groups used the CGMS for 3 days; these values were used to calculate measures of hypoglycemia. Repeated-measures analysis of variance with post hoc comparisons were used to test differences in hemoglobin A1c levels and hypoglycemia between the 2 study groups. RESULTS A total of 128 patients were enrolled in the study. Nineteen discontinued study participation, leaving 51 in the CGMS group and 58 in the SMBG group. No significant differences were noted in demographics or baseline characteristics between the 2 groups. There were no significant differences in hemoglobin A1c levels between the CGMS group and the SMBG group at baseline (9.1% +/- 1.1% vs 9.0% +/- 1.0%, P = .70), and both groups showed statistically significant (P < .001) and similar (P = .95) improvement in hemoglobin A1c levels after 12 weeks of study. However, the CGMS group had a significantly shorter duration of hypoglycemia (sensor glucose, < or = 60 mg/dL) at week 12 of the study (49.4 +/- 40.8 vs 81.0 +/- 61.1 minutes per event, P = .009). CONCLUSION Use of the CGMS to guide therapy adjustments in patients with insulin-treated diabetes reduces the duration of hypoglycemia compared with therapy adjustments guided by SMBG values alone.

Oral antidiabetic agents in type 2 diabetes

The data on the importance of controlling glucose in the hospital setting spans diverse disciplines of medicine. Studies in the areas of stroke, myocardial infarction, bypass surgery, wound and nosocomial infections all point to the tremendous potential to reduce morbidity and mortality among hospitalized patients with hyperglycemia. It is essential that hyperglycemia is identified from the time of hospital admission, and therapy is implemented to achieve and maintain glucose levels as close to normal as possible, regardless of a patients primary reason for admission or previous diabetes status. In the United States, there are more than 4.2 million hospitalizations annually among persons with diabetes [1]. Additionally, as many as 1.5 million persons are hospitalized who have significant hyperglycemia but have no history of diabetes [2]. Identification of and therapeutic interventions to treat hyperglycemia must be initiated in parallel with the presenting medical problem rather than the days after admission, when many of the acute issues have been addressed. The data presented strongly suggest that an early and aggressive approach to the management of hyperglycemia may reduce mortality, morbidity, excessive hospital stays, and added costs.

EFFECT OF HYPERGLYCEMIA ON STROKE OUTCOMES

ABSTRACT Background: Oral antidiabetic agents differ with regard to mechanisms of action, hemoglobin A1c-lowering efficacy, safety, and tolerability. Traditional agents consist of those that enhance insulin secretion (i.e., sulfonylureas and glinides), those that enhance insulin sensitivity (i.e., metformin and the thiazolidinediones), and those that inhibit intestinal carbohydrate absorption (i.e., the α‑glucosidase inhibitors). New oral agents include the dipeptidyl peptidase-4 (DPP‑4) inhibitors, which potentiate the activity of the incretin glucagon-like peptide 1 and enhance glucose-dependent insulin secretion. Scope: We review the characteristics of the traditional oral agents and these newer additions to the pharmaceutical armamentarium. Abstracts and original clinical and preclinical reports in the English language were identified for review based on MEDLINE literature searches (1970–2006) and abstract collections from major diabetes meetings. Conclusions: Traditional oral agents provide significant treatment benefits for diabetic patients, including reduction in risk of microvascular complications. However, most patients with type 2 diabetes do not achieve target glycemic levels with traditional therapies, and these agents are also associated with hypoglycemia, weight gain, and poor tolerability. Oral DPP‑4 inhibitors offer the potential for significant improvement in glycemic control without hypoglycemia or weight gain, although long-term durability of glycemic control (> 52 weeks) has not been established.

DISCOVERY OF A HUMAN PEPTIDE SEQUENCE SIGNALING ISLET NEOGENESIS

OBJECTIVE To review published data about the relationship between hyperglycemia and the outcome of patients with stroke. RESULTS Stroke is the most frequent cause of permanent disability in the Western world and the third leading cause of death among Americans. Each year, more than 500,000 Americans have a cerebrovascular accident. In the medical literature, numerous reports have discussed how hyperglycemia during acute stroke, regardless of a patients prior diabetes status, has been associated with significantly higher morbidity, higher mortality, longer hospital stays, reduced long-term recovery, and diminished ability to return to work. In the United States alone, an estimated

Radiation Therapy of Metastatic Pheochromocytoma: Case Report and Review of the Literature

300 million in additional health-care costs are incurred among hospitalized patients with stroke who also have high blood glucose levels. Treatment of hyperglycemia has safely, successfully, and effectively yielded glucose levels in the normal range in the hospital setting under the direction of specialty physicians and should be implemented in patients with stroke. CONCLUSION Until convincing randomized prospective trials prove that tight glycemic control does not improve stroke outcomes, the overwhelming preponderance of data suggests that aggressive glucose management should be the standard care in all patients with stroke and hyperglycemia.

Distinctions between the islets of mice and men: implications for new therapies for type 1 and 2 diabetes.

OBJECTIVE To identify triggers for islet neogenesis in humans that may lead to new treatments that address the underlying mechanism of disease for patients with type 1 or type 2 diabetes. METHODS In an effort to identify bioactive human peptide sequences that might trigger islet neogenesis, we evaluated amino acid sequences within a variety of mammalian pancreas-specific REG genes. We evaluated GenBank, the Basic Local Alignment Search Tool algorithm, and all available proteomic databases and developed large-scale protein-to-protein interaction maps. Studies of peptides of interest were conducted in human pancreatic ductal tissue, followed by investigations in mice with streptozocin-induced diabetes. RESULTS Our team has defined a 14-amino acid bioactive peptide encoded by a portion of the human REG3a gene we termed Human proIslet Peptide (HIP), which is well conserved among many mammals. Treatment of human pancreatic ductal tissue with HIP stimulated the production of insulin. In diabetic mice, administration of HIP improved glycemic control and significantly increased islet number. Bioinformatics analysis, coupled with biochemical interaction studies in a human pancreatic cell line, identified the human exostoses-like protein 3 (EXTL3) as a HIP-binding protein. HIP enhanced EXTL3 translocation from the membrane to the nucleus, in support of a model whereby EXTL3 mediates HIP signaling for islet neogenesis. CONCLUSION Our data suggest that HIP may be a potential stimulus for islet neogenesis and that the differentiation of new islets is a process distinct from beta cell proliferation within existing islets. Human clinical trials are soon to commence to determine the effect of HIP on generating new islets from ones own pancreatic progenitor cells.

Distinctions between islet neogenesis and β‐cell replication: Implications for reversal of Type 1 and 2 diabetes

Malignant pheochromocytomas are rare tumors, which are considered radioresistant on the basis of little information. We report a patient, with cranial nerve deficits from a pheochromocytoma metastatic to the parasellar region, who promptly responded to radiation therapy (2,500 cGy) with reversal of neurologic deficit. The disease recurred 2 years later and again promptly responded upon treatment to 2,000 cGy. Hepatic metastases were controlled for over 1 year with 3,240 cGy. The radiotherapy of pheochromocytoma and chemodectoma is reviewed, and the similarities between the two kinds of tumor are discussed. We speculate that a higher initial radiation dose might have resulted in a more sustained remission in our patient and recommend doses of 4,000-5,000 cGy if they can be safely administered, in 4-5 weeks for pheochromocytomas.