Mary T Korytkowski

Publications of Mary T Korytkowski

• Hypoglycemia in Hospitalized Patients Treated with Sulfonylureas.

  Authors: Christina M Deusenberry, Kim C Coley, Mary T Korytkowski, Amy C Donihi

  Pharmacotherapy. 05/2012;

  STUDY OBJECTIVE: To identify the incidence of and risk factors associated with hypoglycemia in hospitalized patients taking sulfonylureas. DESIGN: Nested case-control study. SETTING: Tertiary careSTUDY OBJECTIVE: To identify the incidence of and risk factors associated with hypoglycemia in hospitalized patients taking sulfonylureas. DESIGN: Nested case-control study. SETTING: Tertiary care academic medical center. PATIENTS: Adults who received a sulfonylurea during hospitalization between November 1, 2008, and October 31, 2009. Case patients were those who experienced at least one episode of hypoglycemia, defined as a blood glucose level less than 70 mg/dl; potential control patients were those who did not experience hypoglycemia. One hundred seventeen cases were matched in a 1:1 ratio with controls based on sex and the number of days treated with a sulfonylurea in the hospital. For case patients, the index date was defined as the date of first blood glucose level less than 70 mg/dl. The number of days that the patient was taking the sulfonylurea before the index date was determined, and this same number was used to define the index date for the matched controls. MEASUREMENTS AND MAIN RESULTS: Overall, 19% of patients who received a sulfonylurea experienced at least one episode of hypoglycemia: 22% receiving glyburide, 19% receiving glimepiride, and 16% receiving glipizide. Variables included in the multivariate regression were age 65 years or older, glomerular filtration rate (GFR)≤30 ml/min/1.73 m(2) , and treatment with glipizide, glyburide, or concurrent intermediate- or long-acting insulin. Age 65 years or older (odds ratio [OR] 3.07, p < 0.001), intermediate- or long-acting insulin (OR 3.01, p=0.002), and GFR of 30 ml/minute/1.73 m(2) or lower (OR 3.64, p=0.006) were predictors of hypoglycemia. Cases were less likely than controls to receive glipizide (OR 0.44, p=0.005). CONCLUSION: Hospitalized patients at increased risk for sulfonylurea-related hypoglycemia were those aged 65 years or older, those with a GFR of 30 ml/minute/1.73 m(2) or lower, and those who received concurrent intermediate- or long-acting insulin during inpatient sulfonylurea therapy. Sulfonylureas should be avoided or used with caution in these patients.

• U-500 Insulin as a Component of Basal Bolus Insulin Therapy in Type 2 Diabetes.

  Authors: Jolene Brown Lowery, Amy C Donihi, Mary T Korytkowski

  Diabetes technology & therapeutics. 02/2012;

  Abstract Background: Changes in hemoglobin A1c (A1C), weight, and total daily insulin dose (TDD) were investigated following initiation of insulin U-500 (U500) alone or as part of a basal/bolusAbstract Background: Changes in hemoglobin A1c (A1C), weight, and total daily insulin dose (TDD) were investigated following initiation of insulin U-500 (U500) alone or as part of a basal/bolus insulin (BBI) regimen. Subjects and Methods: Records of patients with type 2 diabetes who were prescribed U500 were retrospectively reviewed. Logistic regression analysis was used to investigate relationships between changes in A1C and use of U500 alone or as BBI. Results: Twelve patients were identified as using U500 alone (n=2) or in combination with long-acting (LAI) (n=7) or rapid-acting (RAI) (n=3) insulin. Reductions in A1C (9.5% at baseline vs. 7.7% at 6-9 months, P<0.0001) and increases in weight (128.8±32.7 vs. 131.5±31.3 kg, P<0.014) and TDD (260±111 to 333±106 units/day, P<0.0002) were observed. Concurrent use of LAI or RAI with U500 did not predict improvements in A1C. Conclusions: U500 resulted in improvements in A1C and weight gain and increased TDD when used alone or as part of combination insulin therapy. Further investigations to define the optimal use of U500 are recommended.

• Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline.

  Authors: Guillermo E Umpierrez, Richard Hellman, Mary T Korytkowski, Mikhail Kosiborod, Gregory A Maynard, Victor M Montori, Jane J Seley, Greet Van den Berghe

  The Journal of clinical endocrinology and metabolism. 01/2012; 97(1):16-38.

  The aim was to formulate practice guidelines on the management of hyperglycemia in hospitalized patients in the non-critical care setting. The Task Force was composed of a chair, selected by theThe aim was to formulate practice guidelines on the management of hyperglycemia in hospitalized patients in the non-critical care setting. The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, six additional experts, and a methodologist. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society members, American Diabetes Association, American Heart Association, American Association of Diabetes Educators, European Society of Endocrinology, and the Society of Hospital Medicine reviewed and commented on preliminary drafts of this guideline. Hyperglycemia is a common, serious, and costly health care problem in hospitalized patients. Observational and randomized controlled studies indicate that improvement in glycemic control results in lower rates of hospital complications in general medicine and surgery patients. Implementing a standardized sc insulin order set promoting the use of scheduled basal and nutritional insulin therapy is a key intervention in the inpatient management of diabetes. We provide recommendations for practical, achievable, and safe glycemic targets and describe protocols, procedures, and system improvements required to facilitate the achievement of glycemic goals in patients with hyperglycemia and diabetes admitted in non-critical care settings.

• The adjectives of inpatient glycemic management.

  Authors: Jodie Reider, Mary T Korytkowski

  Current diabetes reports. 12/2011; 12(1):1-3.

• Effect of a targeted glycemic management program on provider response to inpatient hyperglycemia.

  Authors: Amy C Donihi, Jolynn M Gibson, Michelle L Noschese, Monica M DiNardo, Glory L Koerbel, Michelle Curll, Mary T Korytkowski

  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 02/2011; 17(4):552-7.

  To report the results of implementation of a Targeted Glycemic Management (TGM) Service pilot, with the goals of improving clinician awareness of available inpatient glycemic management protocols andTo report the results of implementation of a Targeted Glycemic Management (TGM) Service pilot, with the goals of improving clinician awareness of available inpatient glycemic management protocols and improving responsiveness to and frequency of severe hyperglycemia. Patients with a blood glucose (BG) level ≥300 mg/dL who were hospitalized on a general medicine unit during three 12-week periods before, during, and after the TGM pilot were compared for responsiveness by the primary team, percentage of subsequent BG measurements between 80 and 180 mg/dL, and frequency of subsequent severe hyperglycemia (BG levels ≥300 mg/dL) and hypoglycemia (BG values <70 mg/dL). In comparison with pre-TGM and post-TGM periods, more patients during the TGM pilot had a modification of their glycemic regimen in response to severe hyperglycemia (49% versus 73% versus 50%, before, during, and after TGM, respectively; P = .044), and the percentage of patients with ≥50% of subsequent BG measurements in the desired range (27% versus 53% versus 32%; P = .035) was greatest during the TGM period. The incidence of subsequent severe hyperglycemia (20% versus 9% versus 16%; P = .0004) was lowest during the TGM period; however, the incidence of hypoglycemia was similar in all 3 periods (3.9% versus 3.7% versus 3.7%). These results indicate that a TGM Service can favorably influence glycemic management practices and improve glycemic control, but ongoing intervention is necessary for maintenance of these results.

• Menu selection, glycaemic control and satisfaction with standard and patient-controlled consistent carbohydrate meal plans in hospitalised patients with diabetes.

  Authors: Michelle Curll, Monica Dinardo, Michelle Noschese, Mary T Korytkowski

  Quality & safety in health care. 08/2010; 19(4):355-9.

  Medical nutrition therapy is an important component of glycaemic management in hospitalised patients with diabetes; however, there is a lack of information guiding the ordering of specific meal plansMedical nutrition therapy is an important component of glycaemic management in hospitalised patients with diabetes; however, there is a lack of information guiding the ordering of specific meal plans in this setting. University-affiliated academic medical centre. An administrative decision to gradually replace standard consistent-carbohydrate (CCMP) (standard group) with patient-controlled meal plans (patient-controlled group) presented the opportunity to compare menu selection, adherence to CCMP, glycaemic control and satisfaction as a quality-improvement initiative. Information was obtained from consecutive inpatients with diabetes admitted to units receiving standard (n=30) or patient-controlled meal plans (n=43). Patients received the meal plan according to unit location. No group differences were observed in adherence to CCMP (70% vs 64%, p=0.1), mean capillary blood glucose (CBG) or hyperglycaemia frequency (CBG>180 mg/dl). Hypoglycaemia (CBG<70 mg/dl) occurred more frequently in the patient-controlled group (0.39 vs 3.23%, p=0.04). There were no episodes of severe hypoglycaemia (CBG<40 mg/dl) in either group. The patient-controlled group reported a greater satisfaction and had more opportunities for nutrition education, with a demonstrated improvement in adherence to CCMP following targeted education in six of nine patients with available menu data. The standard group experienced less hypoglycaemia and required less clinician oversight. The patient-controlled group allowed for identification of patients who would benefit from education, required more oversight by nutrition services and reported greater satisfaction with their meal plan. Both meal plans may be appropriate for inpatients with diabetes, provided that a sufficient review is available for patients who make inappropriate selections with the patient-controlled meal plan.

• Impact of patient level factors on the improvement of the ABCs of diabetes.

  Authors: Gretchen A Piatt, Thomas J Songer, Maria M Brooks, Robert M Anderson, David Simmons, Trevor J Orchard, Linda M Siminerio, Mary T Korytkowski, Janice C Zgibor

  Patient education and counseling. 04/2010; 82(2):266-70.

  To determine which patient factors contribute to improvements in the ABCs of diabetes following a multi-faceted diabetes care intervention. A multi-level, cluster design, randomized controlled trialTo determine which patient factors contribute to improvements in the ABCs of diabetes following a multi-faceted diabetes care intervention. A multi-level, cluster design, randomized controlled trial examined the effectiveness of a Chronic Care Model (CCM) intervention in an underserved community (n=119). Improvements in glycemic control were experienced among older subjects (p=0.02), those with higher scores on the WHO-10 Quality of Well-Being Subscale 1 (p=0.05), and those in the CCM group (p=0.04). Insulin use was associated with greater improvements in SBP and DBP. Those taking insulin (p=0.07), and those more satisfied with their diabetes care and ready to make a behavior change (p=0.08) experienced larger improvements in Non-HDLc. Medication treatment intensification (TI) did not significantly impact the ABCs. Psychosocial and sociodemographic factors explained more of the variation in the ABCs than TI, and are important contributors to clinical improvement. Providers may be able to identify and intervene on patients who are at risk for developing diabetes complications and improve the consistency, quality, and effectiveness of patient care.

• Practical implications of the revised guidelines for inpatient glycemic control.

  Authors: Jodie Reider, Amy Donihi, Mary T Korytkowski

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):801-9.

  Substantial observational data has linked hyperglycemia in hospitalized patients with poor patient outcomes. While early studies suggested improved clinical outcomes with interventions targeting nearSubstantial observational data has linked hyperglycemia in hospitalized patients with poor patient outcomes. While early studies suggested improved clinical outcomes with interventions targeting near euglycemia, more recent studies have yielded inconsistent results, with the suggestion of harm with more severe hypoglycemia. The American Association of Clinical Endocrinologists and American Diabetes Association published a revised consensus statement on inpatient glycemic management that takes into account this recent evidence. This statement identifies reasonable, achievable, and safe glycemic targets and describes protocols, procedures, and system improvements necessary to achieve these effectively. These modified glycemic targets promote a rational approach to inpatient glycemic management that minimizes risks associated with uncontrolled hyperglycemia and hypoglycemia. Intravenous insulin infusions are recommended for critically ill patients who experience blood glucose (BG) levels above 140 mg/dl with a target of 140 to 180 mg/dl. Lower BG targets (i.e., 110-140 mg/dl) may be appropriate for patients following cardiac or vascular surgical procedures. In noncritically ill patients, scheduled subcutaneous basal:bolus insulin is the preferred therapy for achieving fasting and preprandial BG below 140 mg/dl and random BG values below 180 mg/dl, with consideration of more or less stringent targets based on a patient's clinical status. Prolonged use of correctional insulin as monotherapy is discouraged. Oral and injectable noninsulin glucose-lowering agents have a limited role for hospital use but may be appropriate for selected noncritically ill patients. Educating personnel about appropriate inpatient glycemic management practices, obtaining reliable and reproducible measures of BG, and careful implementation of standardized protocols can help to ensure patient safety.

• Implementation of standardized instructions for insulin at hospital discharge.

  Authors: Colleen D Lauster, Jolynn M Gibson, Jeannine V DiNella, Monica Dinardo, Mary T Korytkowski, Amy C Donihi

  Journal of hospital medicine (Online). 10/2009; 4(8):E41-2.

• American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control.

  Authors: Etie S Moghissi, Mary T Korytkowski, Monica Dinardo, Daniel Einhorn, Richard Hellman, Irl B Hirsch, Silvio E Inzucchi, Faramarz Ismail-Beigi, M Sue Kirkman, Guillermo E Umpierrez

  Diabetes care. 07/2009; 32(6):1119-31.

• American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control.

  Authors: Etie S. Moghissi, Mary T. Korytkowski, Monica DiNardo, Daniel Einhorn, Richard Hellman, Irl B. Hirsch, Silvio E. Inzucchi, Faramarz Ismail-Beigi, Sue M. Kirkman, Guillermo E. Umpierrez, American Association Clinical Endocrinologists of, American Diabetes Association

  Endocrine practice. 05/2009; 15(4):353-369.

• Insulin therapy and glycemic control in hospitalized patients with diabetes during enteral nutrition therapy: a randomized controlled clinical trial.

  Authors: Mary T Korytkowski, Rose J Salata, Glory L Koerbel, Faith Selzer, Esra Karslioglu, Almoatazbellah M Idriss, Kenneth K W Lee, A James Moser, Frederico G S Toledo

  Diabetes care. 04/2009; 32(4):594-6.

  OBJECTIVE: To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT).OBJECTIVE: To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT). RESEARCH DESIGN AND METHODS: Fifty inpatients were prospectively randomized to receive sliding-scale regular insulin (SSRI) alone (n = 25) or in combination with insulin glargine (n = 25). NPH insulin was added for persistent hyperglycemia in the SSRI group (glucose >10 mmol/l). RESULTS: Glycemic control was similar in the SSRI and glargine groups (mean +/- SD study glucose 8.9 +/- 1.6 vs. 9.2 +/- 1.6 mmol/l, respectively; P = 0.71). NPH insulin was added in 48% of the SSRI group subjects. There were no group differences in frequency of hypoglycemia (1.3 +/- 4.1 vs. 1.1 +/- 1.8%; P = 0.35), total adverse events, or length of stay. CONCLUSIONS: Both insulin strategies (SSRI with the addition of NPH for persistent hyperglycemia and glargine) demonstrated similar efficacy and safety in non-critically ill hospitalized patients with type 2 diabetes during ENT.

• Patient outcomes after implementation of a protocol for inpatient insulin pump therapy.

  Authors: Michelle L. Noschese, Monica M. DiNardo, Amy C. Donihi, Jolynn M. Gibson, Glory L. Koerbel, Melissa Saul, Maja Stefanovic-Racic, Mary T. Korytkowski

  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 01/2009; 15(5):415-424.

  OBJECTIVE: To determine the safety and the results of use of an inpatient insulin pump protocol (IIPP). METHODS: In this quality improvement initiative, review of medical records of bedside capillaryOBJECTIVE: To determine the safety and the results of use of an inpatient insulin pump protocol (IIPP). METHODS: In this quality improvement initiative, review of medical records of bedside capillary blood glucose (CBG) levels and pump-related adverse events was performed on 50 consecutive inpatients admitted to the hospital with continuous subcutaneous insulin infusion (CSII) after implementation of our IIPP. Patients were categorized in 3 groups on the basis of evidence in the medical records for IIPP in combination with inpatient diabetes service consultation (group 1; n = 34), for IIPP alone (group 2; n = 12), or for usual care (group 3; n = 4). Patients identified during hospital admission as using CSII therapy were invited to complete a satisfaction questionnaire for inpatient CSII use. RESULTS: Mean CBG levels were similar among the 3 groups (groups 1, 2, and 3: 173 +/- 43 mg/dL versus 187 +/- 62 mg/dL versus 218 +/- 46 mg/dL, respectively). Although there were more patient-days with blood glucose >300 mg/dL in group 3 (P = .02), there were no significant group differences in the frequency of hypoglycemia (CBG <70 mg/dL). Only 1 pump malfunction and 1 infusion site problem were reported among all study patients. No serious adverse events related to CSII therapy occurred. The majority of patients (86%) reported satisfaction with their ability to continue CSII use in the hospital. CONCLUSION: Patients using CSII as outpatients are candidates for inpatient diabetes self-management. Inexperience with these devices on the part of hospital personnel together with the limited studies of patient experience with CSII in the hospital contributes to inconsistencies in management of these patients. An IIPP provides a standardized and safe approach to the use of CSII in the hospital.

• Diagnosis and minimally invasive resection of an insulinoma: report of an unusual case and review of the literature.

  Authors: Bruce J Gutelius, Mary T Korytkowski, Sally E Carty, Giselle G Hamad

  The American surgeon. 06/2007; 73(5):520-4.

  Insulinomas are rare endocrine tumors that are usually diagnosed by inappropriate elevations in insulin and C-peptide during hypoglycemia. We report a case of a surgically confirmed insulinomaInsulinomas are rare endocrine tumors that are usually diagnosed by inappropriate elevations in insulin and C-peptide during hypoglycemia. We report a case of a surgically confirmed insulinoma diagnosed by a mild elevation in proinsulin with suppressed insulin and C-peptide at the time of hypoglycemia during a supervised fast. A supervised fast with serial measurements of plasma glucose, insulin, and C-peptide was performed in a patient with documented hypoglycemia. Proinsulin was measured at the beginning and end of the fast. Tumor localization was accomplished with spiral CT, magnetic resonance imaging, and endoscopic ultrasound. Minimally invasive tumor resection was performed. The presence of an insulinoma was confirmed on the basis of a minimally elevated proinsulin level with a suppressed insulin level at the time of symptomatic hypoglycemia. Tumor resection was performed without complications, resulting in resolution of the hypoglycemia. This case demonstrates the importance of measuring proinsulin as a routine component of the 72-hour fast for detection of an insulinoma. Even mild elevations in circulating proinsulin can be an independent indicator of aberrant insulin secretion during hypoglycemia. Once the diagnosis of insulinoma is made and tumor localization is achieved, minimally invasive tumor resection is a safe and effective treatment modality.

• Can simple treatment protocols improve the management of hyperglycemia in hospitalized patients?

  Authors: Mary T Korytkowski

  Nature clinical practice. Endocrinology & metabolism. 05/2007; 3(4):328-9.

• Implementing an intravenous insulin infusion protocol in the intensive care unit.

  Authors: Rhonda S Rea, Amy Calabrese Donihi, MaryBeth Bobeck, Peter Herout, Teresa P McKaveney, Sandra L Kane-Gill, Mary T Korytkowski

  American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 03/2007; 64(4):385-95.

  PURPOSE: The implementation of three different insulin protocols in intensive care unit (ICU) settings in two community hospitals and one academic hospital is described. SUMMARY: Each institutionPURPOSE: The implementation of three different insulin protocols in intensive care unit (ICU) settings in two community hospitals and one academic hospital is described. SUMMARY: Each institution possessed a commitment to improve the existing insulin protocols in order to achieve tighter glycemic control for ICU patients. Studies have shown that the maintenance of tight glycemic control provides improved patient outcomes. Obstacles to implementation of the insulin protocols at the institutions were increased staff workload, difficulties in interpreting algorithms, and lack of perceived benefit. In comparing details of the insulin protocols at the academic and community hospitals, it was found that differences were influenced by the type of institution. The differences among the institutions in the implementation of the protocols included the initial physician response to the protocol, the details of each protocol, nursing staff autonomy, and the involvement of the nursing staff in early protocol development. All three institutions had a dedicated pharmacist in the ICU who committed time toward insulin protocol implementation. For an increased likelihood of successful insulin protocol implementation, a full-time dedicated ICU pharmacist should be assigned to participate on multidisciplinary rounds, provide nursing support and education, and collect process measures to monitor and improve the protocol. CONCLUSION: The i.v. insulin infusion protocols developed and implemented in the ICUs at three institutions successfully achieved acceptance and compliance by physicians and nurses. The factors attributed to the success were multidisciplinary involvement, the continuous education of nursing staff, the vigilant involvement of a pharmacist, and flexibility in revising the protocol.

• The metabolic syndrome is associated with reduced central serotonergic responsivity in healthy community volunteers.

  Authors: Matthew F Muldoon, Rachel H Mackey, Mary T Korytkowski, Janine D Flory, Bruce G Pollock, Stephen B Manuck

  The Journal of clinical endocrinology and metabolism. 02/2006; 91(2):718-21.

  CONTEXT: The pathobiology of the metabolic syndrome remains unclear. The central nervous system is likely to be involved via regulation of eating, physical activity, blood pressure, and metabolism.CONTEXT: The pathobiology of the metabolic syndrome remains unclear. The central nervous system is likely to be involved via regulation of eating, physical activity, blood pressure, and metabolism. OBJECTIVE: The objective of this study was to test the hypothesis that low central serotonergic activity is associated with the metabolic syndrome. DESIGN, SETTING, PARTICIPANTS: This was a cross-sectional study of 345 healthy community volunteers, aged 30-55 yr, not taking medications for hypertension, lipid disorders, or diabetes. OUTCOME MEASURES: Central serotonergic responsivity was assessed with the iv citalopram challenge test. The serum prolactin area under the curve (AUC) over 150 min was calculated, and all analyses were adjusted for age, sex, plasma citalopram concentration, and baseline prolactin. The metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Insulin resistance was estimated by homeostasis model assessment. RESULTS: Compared with other individuals, persons meeting either NCEP or IDF criteria for the metabolic syndrome had lower mean prolactin responses (P < 0.05 for both). Using logistic regression, a decrease in prolactin AUC of 1 sd (-13.6 ng/ml.h) more than doubled the odds of having the metabolic syndrome (NCEP criteria: odds ratio, 2.38; 95% confidence interval, 1.14-4.97; P = 0.02; IDF criteria: odds ratio, 2.80; 95% confidence interval, 1.48-5.30; P = 0.002). Finally, the prolactin AUC was negatively associated with insulin resistance (beta = -0.03, P = 0.02). CONCLUSIONS: Corroborating previous evidence, the metabolic syndrome was associated with diminished brain serotonergic activity as reflected in a comparative blunting of the prolactin response to a selective serotonergic challenge. This association may have implications for the etiology, prevention, and treatment of the metabolic syndrome.

• Does androgen excess contribute to the cardiovascular risk profile in postmenopausal women with type 2 diabetes?

  Authors: Mary T Korytkowski, Esther I Krug, Margaret A Daly, Louise Deriso, John W Wilson, Stephen J Winters

  Metabolism: clinical and experimental. 12/2005; 54(12):1626-31.

  The purpose of this study was to determine if postmenopausal women with type 2 diabetes have clinical and biochemical evidence of androgen excess as a potential contributor to an increase in risk forThe purpose of this study was to determine if postmenopausal women with type 2 diabetes have clinical and biochemical evidence of androgen excess as a potential contributor to an increase in risk for coronary heart disease when compared with women without diabetes. Fasting glucose, insulin, lipids, sex hormone-binding globulin (SHBG), and sex steroids (from pooled samples) (total testosterone and free testosterone [non-SHBG-T], androstenedione [A-dione], total estrogens) were measured at baseline in 16 postmenopausal women with type 2 diabetes treated with diet or a sulfonylurea and 17 age-matched controls. Measurements of glucose, insulin, and sex steroids were repeated at hourly intervals for 3 hours after oral glucose administration. Hirsutism scores and insulin sensitivity (homeotasis model assessment [HOMA] insulin [SI]) were obtained. Women with type 2 diabetes were more hyperglycemic, hyperinsulinemic, and insulin-resistant (HOMA SI, 46.7 +/- 7.0 vs 12.9 +/- 2.0, P < .001), and had higher total to high-density lipoprotein cholesterol (TC/HDL) ratios, lower SHBG (20.8 +/- 3.5 vs 59.3 +/- 14.4 nmol/L, P < .05), higher non-SHBG-T (0.225 +/- 0.025 vs 0.135 +/- 0.021 nmol/L, P < .05), and higher hirsutism scores (1.1 +/- 0.3 vs 0.3 +/- 0.2, P = .004) than those without diabetes. No changes in sex steroids occurred after the oral glucose challenge. HOMA SI and area under the curve for glucose correlated significantly with SHBG (r = -0.42), non-SHBG-T (r = 0.40), and TC/HDL (r = 0.41) (all P < .05) in the combined groups. Postmenopausal women with type 2 diabetes have both clinical and biochemical evidence of androgen excess that may contribute to more adverse cardiovascular risk profiles.

• Sulfonylurea treatment of type 2 diabetes mellitus: focus on glimepiride.

  Authors: Mary T Korytkowski

  Pharmacotherapy. 06/2004; 24(5):606-20.

  Sulfonylureas, which have evolved through two generations since their introduction nearly 50 years ago, remain the most frequently prescribed oral agents for treatment of patients with type 2Sulfonylureas, which have evolved through two generations since their introduction nearly 50 years ago, remain the most frequently prescribed oral agents for treatment of patients with type 2 diabetes mellitus. Glyburide, glipizide, and glimepiride, the newest sulfonylureas, are as effective at lowering plasma glucose concentrations as first-generation agents but are more potent, better tolerated, and associated with a lower risk of adverse effects. Differences in their binding affinity to the beta-cell sulfonylurea receptor have been described, with preservation of cardioprotective responses to ischemia with glimepiride. Clinical studies have shown glimepiride to be safe and effective in reducing fasting and postprandial glucose levels, as well as glycosylated hemoglobin concentrations, with dosages of 1-8 mg/day. In comparative trials, glimepiride was as effective in lowering glucose levels as glyburide and glipizide, but glimepiride was associated with a reduced likelihood of hypoglycemia and a smaller increase in fasting insulin and C-peptide levels than glyburide, and a more rapid lowering of fasting plasma glucose levels than glipizide. Glimepiride also improves first-phase insulin secretion, which plays an important role in reducing postprandial hyperglycemia. Insulin secretagogues, specifically glimepiride, merit consideration as first-line therapy for patients with type 2 diabetes.

• Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity.

  Authors: Matthew F Muldoon, Rachel H Mackey, Katherine V Williams, Mary T Korytkowski, Janine D Flory, Stephen B Manuck

  The Journal of clinical endocrinology and metabolism. 02/2004; 89(1):266-71.

  The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances inThe metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotonin-releasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend = 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10-3.83; P = 0.002) and 5.70 (95% confidence interval, 1.69-19.25; P = 0.005), according to the definitions of the National Cholesterol Education Program and the World Health Organization, respectively. These findings reveal a heretofore unrecognized association between reduced central serotonergic responsivity and the metabolic syndrome.