Liraglutide as Additional Treatment to Insulin in Obese Patients with Type 1 Diabetes Mellitus

ObjectiveBecause approximately 40% of patients with type 1 diabetes have the metabolic syndrome, we tested the hypothesis that addition of liraglutide to insulin in obese patients with type 1 diabetes will result in an improvement in plasma glucose concentrations, a reduction in hemoglobin A1c (HbA1c), a fall in systolic blood pressure, and weight loss.MethodsThis is a retrospective analysis of data obtained from 27 obese patients with type 1 diabetes treated with liraglutide in addition to insulin. Patients were also treated for hypertension. Paired t tests were used to compare the changes in HbA1c, insulin doses, body weight, body mass index, 4-week mean blood glucose concentrations (28-day insulin pump mean blood glucose), blood pressure, and lipid parameters prior to and 180 ± 14 days after liraglutide therapy.ResultsMean glucose concentrations fell from 191 ± 6 to 170 ± 6 mg/dL (P = .002). HbA1c fell from 7.89 ± 0.13% to 7.46 ± 0.13% (P = .001), without an increase in frequency of hypoglycemia. Mean body weight fell from 96.20 ± 3.68 kg to 91.56 ± 3.78 kg (P<.0001). Daily total and bolus doses of insulin fell from 73 ± 6 to 60 ± 4 (P = .008) units and from 40 ± 5 to 29 ± 3 units (P = .011), respectively. Mean systolic blood pressure fell from 130 ± 3 to 120 ± 4 mm Hg (P = .020).ConclusionAddition of liraglutide to insulin in obese patients with type 1 diabetes mellitus leads to improvements in glycemic control and HbA1c and to reductions in insulin dose, systolic blood pressure, and body weight. (Endocr Pract. 2013;19:963-967)     

Effect of High-Dose Vitamin D Repletion on Glycemic Control in African-American Males with Prediabetes and Hypovitaminosis D

Objective: This double-blind, randomized, controlled trial evaluated whether 12 months of high-dose vitamin D2 supplementation improved insulin sensitivity and secretion and glycemic status.Methods: African-American males (AAM) with prediabetes (glycosylated hemoglobin [A1C] 5.7-6.4%), hypovitaminosis D (25-hydroxyvitamin D [25OHD] 5-29 ng/mL), and prevalent medical problems were supplemented with vitamin D3 (400 IU/day) and then randomized to weekly placebo or vitamin D2 (50,000 IU). The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from an oral glucose tolerance test [OGTT]) after 12 months of treatment. Secondary outcomes included other glycemic indices, A1C, and incident diabetes.Results: Baseline characteristics were similar in vitamin D-supplemented (n = 87) and placebo (n = 86) subjects completing the trial with average concentrations 14.4 ng/mL, 362 mL × min^-1 × m^-2, and 6.1% for 25OHD, OGIS and A1C, respectively. After 12 months, the vitamin D-supplemented group had a change in serum 25OHD +35 versus +6 ng/mL for placebo, P<.001; OGIS +7.8 versus -16.0 mL × min^-1 × m^-2 for placebo, P = .026; and A1C -0.01 versus +0.01% for placebo, P = .66. Ten percent of subjects in both groups progressed to diabetes. A posthoc analysis of participants with baseline impaired fasting glucose (IFG) showed that more subjects in the vitamin D subgroup (31.6%) than placebo (8.3%) returned to normal glucose tolerance, but the difference did not reach significance (P = .13).Conclusion: The trial does not provide evidence that 12 months of high-dose D2 repletion improves clinically relevant glycemic outcomes in subjects with prediabetes and hypovitaminosis D (NCT01375660).Abbreviations: AAM = African-American males A1C = glycosylated hemoglobin BMI = body mass index D2 = ergocalciferol D3 = cholecalciferol IFG = impaired fasting glucose IGT = impaired glucose tolerance JBVAMC = Jesse Brown VA Medical Center OGIS = oral glucose insulin sensitivity index OGTT = oral glucose tolerance test 25OHD = 25-hydroxyvitamin D VHA = Veterans Health Administration     

Minimal Reduction in Insulin Dosage with Pramlintide Therapy When Pretreatment Near-Normal Glycemia is Established and Square-Wave Meal Bolus is Used

ObjectiveTo evaluate the effect of near-normal glucose control before initiation of pramlintide therapy and square-wave meal bolus on self-reported hypoglycemia and the percentage change in dosing parameters after attaining the maximum pramlintide dosage.MethodsIn this prospective study, insulin pump–treated patients with type 1 diabetes had insulin dosages optimally titrated on the basis of daily continuous glucose monitoring (CGM). Pramlintide therapy was initiated, and the dosage was increased 15 mcg/meal per week. Insulin dosage was adjusted during 30-minute visits after review of self-monitored blood glucose records, adverse effects, and hypoglycemia diary. Within 2 weeks of achieving a pramlintide dosage of 60 mcg/meal, the second CGM–guided insulin dosage adjustment was done. The primary end point was the percentage change in total basal insulin dosage (TBD) from baseline. The secondary end points were the percentage change in the insulin to carbohydrate ratio (ICR) and the assessment of symptoms of nausea and hypoglycemia during the pramlintide dosing escalation.ResultsNine patients were enrolled. The difference between before and during CGM–guided insulin dosing was a mean (± standard deviation) TBD change of -11.2 ± 13.2% (P = 0.023) and mean ICR change of 7.8 ± 13.4% (P = 0.053). Pramlintide was well tolerated and resulted in decrease in weight and hemoglobin A_1c values. Hypoglycemia occurred in 6 patients during the study; the assistance of another person was not required in any of these cases. No hypoglycemia was reported in the first week of starting pramlintide. Mild to moderate nausea was reported in 6 patients during the titration phase.ConclusionsPatients with near-normal glucose control who use a square-wave bolus may not need initial bolus dosage reduction. With weight loss, small adjustments in both TBD and ICR may be required. Greater incidence of hypoglycemia seen in previous studies may in part be due to mismatched insulin dosing. (Endocr Pract. 2009;15:229-233)     

U500 Regular Insulin use in Insulin-Resistant type 2 Diabetic Veteran Patients

ObjectiveTo evaluate the use of U500 regular insulin therapy in insulin-resistant patients with type 2 diabetes mellitus who were previously treated with high-dosage U100 insulin regimens.Methods:At a large Veterans Affairs medical center, a retrospective chart review was performed of all patients whose U100 insulin regimens were converted to U500 regular insulin regimens using a protocol to ensure patient safety. Patients were followed up for longer than 6 months. Data reviewed included total daily dosage of insulin before and after regimen conversion and changes in hemoglobin A1c, body weight, lipids, and episodes of severe hypoglycemia.ResultsFifty-three patients met inclusion criteria. Average hemoglobin A1c level on U100 insulin regimens was 9.1 ± 1.7%, which decreased to 8.1 ± 1.3% (P < .001) after an average of 20 months (range, 6-52 months) on U500 insulin. The total daily insulin dosage at study end was not significantly greater on U500 (415 ± 166 units/day) than on U100 insulin (391 ± 120 units/day) (P = .34). Body weight did not change significantly (134 ± 29 kg vs 136 ± 30 kg, P = .18). There was a 20-mg/dL decrease in total cholesterol (P = .014). Triglyceride values decreased by 97 mg/dL (P = .005). Eight episodes of severe hypoglycemia were documented in patients treated with U500 insulin, but this was similar to the incidence in these same patients while treated with U100 insulin.ConclusionWe conclude that U500 insulin can be safely and effectively used in insulin-resistant patients with type 2 diabetes followed up at a large Veterans Affairs medical center using a protocol that ensures patients are thoroughly educated and carefully monitored. (Endocr Pract. 2012;18:34-38)     

Ethnic disparity in hemoglobin A1c levels among normoglycemic offspring of parents with type 2 diabetes mellitus

ObjectiveTo investigate the racial/ethnic disparities in hemoglobin A_1c levels among nondiabetic persons with similar parental history of type 2 diabetes mellitus.MethodsWe studied a community-based sample of adult offspring of parents with type 2 diabetes mellitus. Measurements included anthropometry, hematology assessments, serial fasting plasma glucose, oral glucose tolerance testing, plasma insulin, hemoglobin A_1c, insulin sensitivity, and b-cell function, using a homeostasis model assessment.ResultsThe study included 302 participants (135 white, 167 black). Compared with white participants, black participants had lower fasting plasma glucose levels (91.9 ± 0.51 mg/dL vs 93.6 ± 0.50 mg/dL, P = .015), lower area under the curve of plasma glucose during oral glucose tolerance testing (P = <.001), higher body mass index (31.1 ± 0.61 kg/m² vs 28.5 ± 0.57 kg/m², P = <.001), and similar insulin sensitivity and b-cell function. Hemoglobin A_1c was higher in black participants than in white participants (5.68 ± 0.033% vs 5.45 ± 0.028%, P <.001). The absolute black-white difference in hemoglobin A_1c level of approximately 0.22% persisted after adjusting for age, hemoglobin, hematocrit, body mass index, waist circumference, fasting plasma glucose, glucose area under the curve, and other covariates.ConclusionsAmong healthy offspring of parents with type 2 diabetes mellitus in this study, African American participants had higher hemoglobin A_1c levels than white participants after adjusting for age, adiposity, blood glucose, and known variables. Thus, plasma glucose level is more valid than hemoglobin A_1c for diagnosing prediabetes or diabetes in black persons. (Endocr Pract. 2012; 18:356-362)     

Effect of Dexamethasone on Insulin Secretion: Examination of Underlying Mechanisms

ObjectiveTo study the mechanism of increased insulin secretion in response to short-term administration of dexamethasone.MethodsMale Wistar rats were injected intraperitoneally with dexamethasone (dexamethasone; 200 mcg/kg body weight per day) or saline for 3 consecutive days. Insulin secretion in response to glucose, ionomycin, and KCl was quantified in islets isolated from the animals, and the amount of glucokinase was measured by Western blot.ResultsDexamethasone-treated animals had 1.18-fold higher fasting blood glucose concentration and 6.5-fold increase in fasting serum insulin concentration compared with findings from animals injected with saline. Compared with islets isolated from control rats, islets from dexamethasone-treated rats secreted more insulin at 60 minutes in response to 5.5 mM glucose (416.4 vs 115.6 fmoles/10 islets, P = .011) and in response to 16.6 mM glucose (985.5 vs 520.6 fmoles/10 islets, P = .014); no change in insulin secretion was observed at 10 minutes. Insulin secretion from islets of dexamethasone-treated rats and control rats was not differentially augmented in response to either ionomycin or potassium chloride. Glucokinase expression was not altered by treatment with dexamethasone.ConclusionsAugmentation of insulin secretion in response to glucose in the pancreatic islets from dexamethasone-treated rats is preserved in islets studied in vitro. The increase in glucose-stimulated insulin secretion appears to be mediated by steps upstream to β -cell membrane depolarization and the attended increase in intracellular calcium in the signaling pathway of insulin secretion. (Endocr Pract. 2010;16:763-769)     

Dpp4 Inhibitor Sitagliptin As A Potential Treatment Option In Metformin-Intolerant Obese Women With Polycystic Ovary Syndrome: A Pilot Randomized Study

Objective: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated the dipeptidyl peptidase 4 inhibitor sitagliptin as a potential treatment option in metformin-intolerant PCOS.Methods: We conducted a 12-week, prospective, randomized, open-label study with 30 obese metformin-intolerant women with PCOS (age 35.0 ± 7.2 years; body mass index, 36.9 ± 5.5 kg/m²). After metformin withdrawal, they were randomized to lifestyle intervention and sitagliptin 100 mg daily (SITA) or lifestyle intervention alone as controls (CON). All participants underwent anthropometric and endocrine measurements and oral glucose tolerance testing. Model-derived indexes of insulin resistance and beta-cell function were calculated.Results: SITA improved beta-cell function as assessed by the homeostasis model assessment for beta-cell function index (HOMA-B) of 45.9 ± 35.8 (P = .001), modified beta-cell function index (MBCI) of 7.9 ± 7 (P = .002), and quantitative insulin-sensitivity check index (QUICKI) of -0.03 ± 0.03 (P = .002). By contrast, beta-cell function decreased in CON. The between-group differences were significant for HOMA-B (P = 0.001), MBCI (P = .010), and QUICKI (P = .025). The conversion rate to impaired glucose homeostasis was prevented in SITA: 3 of 15 subjects had impaired glucose tolerance (IGT) before and after the study. In CON, none had type 2 diabetes (T2D), and 4 had IGT at the beginning. After 12 weeks, IGT was observed in 2 and T2D in 3 subjects.Conclusion: SITA improved beta-cell function and prevented a conversion to IGT and T2D in metformin-intolerant obese PCOS patients.Abbreviations: BMI = body mass index; DPP-4 = dipeptidyl peptidase-4; DXA = dual energy X-ray absorptiometry; GIP = glucose-dependent insulinotropic peptide; GLP-1 = glucagon-like peptide-1; HOMA-B = homeostasis model assessment for beta-cell function; HOMA-IR = homeostasis model assessment of insulin resistance; IAI = insulin action index; IGT = impaired glucose tolerance; IR = insulin resistance; MBCI = modified beta-cell function index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index; PCOS = polycystic ovary syndrome; SHBG = sex hormone–binding globulin; T2D = type 2 diabetes     

Effect of Sitagliptin on Post-Prandial Glucagon and GLP-1 Levels in Patients With Type 1 Diabetes: Investigator-Initiated,Double-Blind,Randomized, Placebo-Controlled Trial

ObjectivePeripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin (dipeptidyl peptidase-IV [DPP-IV] inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon.MethodsThis investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16 weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in glycated hemoglobin (A1c), CGM data, insulin dose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and C-peptide levels.ResultsThere were no differences at screening between groups; however, after a 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<.001) and GIP levels lower (P = .03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 versus 16.0 ± 1.8; P = .006) in the sitagliptin group at 16 weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16 weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose, and time spent in hyperglycemia.ConclusionSitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose, or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia, which needs further evaluation. (Endocr Pract. 2013;19:19-28)     

Markedly Delayed Insulin Secretion and a High Rate of Undetected Overt Diabetes Characterize Glucose Metabolism in Adult Patients with Cystic Fibrosis After Lung Transplantation

Objective: Cystic fibrosis–related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT).Methods: Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index &lsqb;BMI] 21.5 ± 3.3 kg/m²) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m²; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed.Results: In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m²*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m²*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m²*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels.Conclusion: Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism.Abbreviations: AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis–related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index     

A Retrospective Study Comparing Neutral Protamine Hagedorn Insulin With Glargine As Basal Therapy In Prednisone-Associated Diabetes Mellitus In Hospitalized Patients

ObjectiveTo compare glycemic outcomes in hospitalized patients with or without type 2 diabetes mellitus receiving neutral protamine Hagedorn insulin (NPH) vs glargine as basal insulin for management of glucocorticoid-associated hyperglycemia.MethodsWe conducted a retrospective review of electronic medical records in prednisone-treated adult patients with hyperglycemia in a university hospital. Consecutive patients were selected in both the NPH and glargine cohorts using inclusion and exclusion criteria. Baseline characteristics were assessed in each cohort. Glycemic outcomes were analyzed by comparing fasting blood glucose, mean daily blood glucose concentration, median daily blood glucose concentration, and the number of hypoglycemic episodes on a prespecified index day.ResultsOne hundred twenty patients were included: 60 patients in the NPH cohort and 60 patients in the glargine cohort. The weight-based insulin requirement was lower in the NPH cohort than in the glargine cohort (0.27 ± 0.2 units/kg vs 0.34 ± 0.2 units/kg [P = .04] for basal insulin and 0.26 ± 0.2 units/kg vs 0.36 ± 0.2 units/kg [P = .03] for bolus insulin). NPH and glargine cohorts were similar regarding age, sex, race, body mass index, hemoglobin A_1c, serum creatinine, and prednisone dosage. Glycemic outcomes in the NPH cohort compared with outcomes in the glargine cohort were similar regarding mean fasting blood glucose concentration (134 ± 49 mg/dL vs 139 ± 54 mg/dL [P = .63]), mean daily blood glucose (167 ± 46 mg/dL vs 165 ± 52 mg/dL [P = .79]), median blood glucose (160 ± 49 mg/dL vs 159 ± 57 mg/dL [P = .90]), and number of hypoglycemic episodes per day (0.12 ± 0.3 vs 0.10 ± 0.3 [P = .77]).ConclusionsNPH and glargine appear to be equally effective as basal insulin in the management of hyperglycemia in hospitalized patients receiving prednisone. However, the total daily insulin doses used were lower in the NPH cohort. (Endocr Pract. 2012;18:712-719)     

Metformin and Improvement of the Hepatic Insulin Resistance Index Independent of Anthropometric Changes

ObjectiveTo determine the change in the hepatic insulin resistance index (HIRI) after metformin treatment.MethodsIn this retrospective cohort study, Mexican mestizo patients with a body mass index (BMI) of 25 kg/m² or greater were evaluated. Participants were classified into 2 groups: patients who received metformin and patients who did not. Both groups were followed up for a median of 6 months (range. 4-10 months). The HIRI was calculated at baseline and at follow-up in both groups. We evaluated the independent effect of metformin on HIRI after adjustment for the difference in basal and final values (DELTA) of BMI, waist circumference, glucose, and insulin.ResultsA total of 71 patients were enrolled (51 [72%] female). Forty-one patients received metformin and 30 patients did not. Mean age was 36.3 ± 12.2 years and mean BMI was 42.2 ± 10.7 kg/m². After metformin treatment. HIRI significantly decreased from 38 ± 10.7 to 34.7 ± 9.5 (P = .03). In contrast. the control group had a nonsignificant increase in HIRI (37.6 ± 11.7 to 40.0 ± 14.0, P = .22). Weight significantly decreased in both groups (group 1: 114.6 ± 33.8 kg to 107.6 ± 28.9 kg, P < .01; group 2: 104.8 ± 28.5 kg to 98.9 ± 26.0 kg, P < .01). After BMI adjustment, the total metformin dosage correlated negatively with HIRI (r = –0.36, P = .03). Using a linear regression model (F = 6.0, r² = 0.37, P = .002) adjusted for DELTA BMI and DELTA waist circumference. the administration of metformin resulted in independent improvement in the HIRI level (standardized β = –0.29, t = –2.0, P = .04).ConclusionsMetformin improves HIRI independently of anthropometric changes. In persons with elevated HIRI levels, metformin may be considered among the treatment options. (Endocr Pract. 2012;18:8-16)     

Evaluation of Total Daily Dose and Glycemic Control for Patients Taking U-500 Regular Insulin Admitted to the Hospital

Objective: Patients using U-500 regular insulin are severely insulin resistant, requiring high doses of insulin. It has been observed that a patient's insulin requirements may dramatically decrease during hospitalization. This study sought to systematically investigate this phenomenon.Methods: We performed a retrospective chart review of patients with U-500 insulin outpatient regimens who were admitted to the San Antonio Military Medical Center over a 5-year period. Each patient's outpatient total daily dose (TDD) of insulin was compared to the average inpatient TDD. The outpatient estimated average glucose (eAG) was calculated from the glycated hemoglobin (HbA1c) and compared to the average inpatient glucose.Results: There were 27 patients with a total of 62 separate admissions. The average age was 64.4 years, with a mean body mass index of 38.9 kg/m² and eAG of 203 mg/dL (HbA1c, 8.7%, 71.6 mmol/mol). All patients were converted from U-500 to U-100 upon admission. The average inpatient TDD of insulin was 91 units, versus 337 units as outpatients (P<.001). Overall, 89% of patients received ≤50% of their outpatient TDD. The average inpatient glucose was slightly higher than the outpatient eAG, 234 mg/dL versus 203 mg/dL (P = .003).Conclusion: U-500 insulin is prone to errors in the hospital setting, so conversion to U-100 insulin is a preferred option. Despite a significant reduction in insulin TDD, these patients had clinically similar glucose levels. Therefore, patients taking U-500 insulin as an outpatient can be converted to a U-100 basal-bolus regimen with at least a 50% reduction of their outpatient TDD.Abbreviations:BG = blood glucoseeAG = estimated average glucoseHbA1c = glycated hemoglobinNPO = nil per osSPSS = Statistical Package for the Social SciencesTDD = total daily dose     

Clinical Experience with U500 Insulin: Risks and Benefits

ObjectiveTo describe our clinical experience with U500 insulin in insulin-resistant patients, including change in glucose control, body weight, insulin dose, and hypoglycemic episodes.MethodsIn September 2010, we undertook a retrospective chart review of patients who had U500 insulin in their medication list in the preceding 2 years who were treated in the endocrinology section at Dartmouth Hitchcock Medical Center. Glycosylated hemoglobin (A1C), body weight, and insulin dosage were documented before U500 insulin introduction, after 6 months of U500 insulin use, and at the last clinic visit when the patient was still taking U500 insulin. Hypoglycemic episodes and number of daily injections were recorded.ResultsRecords of 53 patients were analyzed, one of the largest reports of U500 insulin use published to date. The mean A1C level decreased from 10.1% before U500 insulin was initiated to 9.1% after 6 months of U500 use to 8.6% at the last follow-up visit (mean follow-up was 36.6 ± 24 months). At the last charted visit, body weight increased by a mean of 6.8 kg and insulin dosage increased by a mean of 0.44 units/kg. We observed a significant increase in the number of nonsevere hypoglycemic episodes and a decrease in the number of daily injections.ConclusionPatients with uncontrolled, severely insulin-resistant diabetes can be satisfactorily treated with U500 insulin with the potential to improve glycemic control. An increase in body weight, insulin dosage, and the number of nonsevere hypoglycemic episodes was observed. (Endocr Pract. 2012;18:56-61)     

Evaluation of Diabetes Management In A Rural Community Hospital

ObjectiveTo evaluate the effectiveness of implementing standardized insulin protocols in a small, rural community hospital.MethodsThis retrospective review was performed on charts of 300 inpatients who received insulin treatment while hospitalized between January 1, 2006, and June 30, 2006. For patients who met the inclusion criteria, the collected information included the following: serum glucose level at hospital admission, glucose level that initiated the treatment protocol, time-to-fasting euglycemia, time-to-random euglycemia, and method of insulin administration. Comparisons were performed between the effectiveness of the new insulin protocols and routine insulin treatment orders.ResultsA total of 168 patients met the study inclusion criteria. The mean glucose concentration that triggered initiation of insulin treatment was 262 mg/dL, which is significantly higher (P < .001) than levels recommended by the American Diabetes Association (ADA) and the American College of Endocrinology (ACE). There was a statistically significant relationship (P = .007) between time-to-fasting euglycemia and length of hospital stay. Implementation of the standardized insulin protocol did not improve the achievement of fasting euglycemia (P = .753). Most patients never reached the target glucose level goals despite the use of standardized protocol.ConclusionSignificant delays in initiating the insulin protocol and frequent failure in achieving target glucose levels demonstrate delayed recognition of hyperglycemia by hospital staff as well as ineffective use of standardized insulin protocols. Protocol improvement and increased hospital staff education concerning appropriate hospital target glucose levels are required to achieve ADA/ACE recommendations in small community hospitals. (Endocr Pract. 2008;14:50-57)     

Efficacy and Safety of Insulin Lispro in Obese Patients with Type 2 Diabetes: A Retrospective Meta-Analysis of 7 Randomized Controlled Trials

ObjectiveTo evaluate the efficacy and safety of insulin lispro in the treatment of patients with type 2 diabetes (T2DM) who had a body mass index (BMI) ≥ 30 kg/m² (obese) compared with patients with BMIs < 30 kg/m² (nonobese).MethodsA retrospective analysis of predefined endpoints from 7 randomized clinical trials of T2DM patients treated with insulin lispro was performed. The primary efficacy measure was to assess the noninferiority of insulin lispro in obese patients versus nonobese patients as measured by the change in hemoglobin A1C (HbA_1c) from baseline to Month 3 (n = 1,518), using a noninferiority margin of 0.4%. The secondary measures included overall hypoglycemia incidence and event rates and relative change in body weight.ResultsMean changes in HbA_1c from baseline (9.06% for obese and 8.92% for nonobese) to Month 3 were similar for obese patients (–1.03%) and nonobese (–1.02%), with a least squares (LS) mean difference (95% confidence interval [CI]) of –0.05% (–0.17%, 0.07%; P = .384). The overall incidence of hypoglycemia (53% vs. 63%; P < .001) and rate of hypoglycemia (0.93 vs. 1.76 events per 30 days; P < .001) was significantly lower in obese patients compared with nonobese patients. The 2 BMI cohorts did not demonstrate a significant difference in mean percent changes in body weights (LS mean difference = 0.4% [–0.2%, 0.9%]; P = .202).ConclusionObese patients with T2DM treated with insulin lispro were able to achieve the same level of glycemic control as their nonobese counterparts, with some evidence supporting a reduced risk of hypoglycemia. (Endocr Pract. 2014;20:389-398)     

Gestational Weight Gain as an Independent Risk Factor for Macrosomia in Women with Intermediate State Gestational Blood Glucose

Objective: Macrosomia is closely associated with gestational diabetes mellitus (GDM) but its relationship with maternal intermediate state gestational blood glucose (ISGBG; normal fasting blood glucose and 7.8 mmol/L <1 hour blood glucose &lsqb;BG] <10 mmol/L or 6.7 mmol/L <2 hour BG <8.5 mmol/L) is unclear. Here, we analyzed the clinical characteristics and pregnancy outcomes and explored risk factors for macrosomia in women with ISGBG.Methods: A total of 847 women with normal glucose tolerance gestation, 330 with ISGBG, and 99 with GDM were included. Maternal and fetal clinical data were collected and 3-point BG following oral glucose tolerance test, fasting insulin, glycated hemoglobin, and blood lipids profile were measured.Results: The incidence rate of macrosomia among the neonates of women with ISGBG was as high as 10.9%. In the ISGBG group, prepregnancy body mass index (BMI), gestational weight gain (GWG) and the proportion of women with excessive GWG (eGWG) were significantly higher in women with macrosomia compared with those who delivered a normal weight neonate. In women with ISGBG, neonate weight was positively correlated with maternal prepregnancy weight (r = 0.183, P<.01), prepregnancy BMI (r = 0.135, P<.01), and GWG (r = 0.255, P<.01), and negatively correlated with high-density lipoprotein cholesterol (r = -0.172, P<.01). Nonetheless, only eGWG was an independent risk factor (odds ratio = 3.18, 95% confidence interval = 1.26 to 7.88, P<.05) for macrosomia. The risk of macrosomia in pregnant women with prepregnancy BMI <25 kg/m² or BMI ≥25 kg/m² and eGWG was 3.39 and 3.27 times, respectively.Conclusion: The incidence rate of macrosomia is increased in women with ISGBG and eGWG is the strongest independent risk factor. In order to reduce the risk for macrosomia, timely lifestyle intervention to promote appropriate weight gain during pregnancy deserves evaluation.Abbreviations: AUC = area under the curve; BG = blood glucose; 1 hour BG = 1 hour blood glucose after OGTT; 2 hour BG = 2 hour blood glucose after OGTT; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; FBG = fasting blood glucose; FINS = fasting insulin; GDM = gestational diabetes mellitus; HbA1c = glycated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance index; ISGBG = intermediate state gestation blood glucose; LDL-C = low-density lipoprotein cholesterol; Ln = natural logarithm; MLBW = mature low birth weight; NGTG = normal glucose tolerance gestation; OGTT = oral glucose tolerance test; OR = odds ratio; SD = standard deviation     

Use of Insulin Pump Therapy in Patients with Type 2 Diabetes After Failure of Multiple Daily Injections

ObjectiveTo determine the effectiveness of insulin pump use (continuous subcutaneous insulin infusion; CSII) in patients with type 2 diabetes (DM2) who have failed multiple daily injection (MDI) therapy.MethodsIn this retrospective study, charts of patients with DM2 who were started on CSII after failure of MDI were reviewed. Patients were categorized as primarily manual (fixed) bolus users or calculated (using pump software) bolus users. The change in hemoglobin A1c (HbA1c), weight, and basal insulin dose from baseline to 6 months was determined.ResultsFifty-seven patients (20 men and 37 women) ranging in age from 13 to 71 were identified in the study. A significant reduction in HbA1c was observed from 8.75 to 7.69% (P<.001). There was an increase in body mass index (BMI) from a mean of 36.53 to a mean of 37.21. A decrease in basal insulin requirement per kilogram of weight (−0.10 U/kg) was noted (P = .03). Seven patients using U-500 insulin in the pump also had a significant decrease in HbA1C of 1.1 % (P<.001), along with a 0.071 U/kg drop in basal insulin requirements (P<.001). When comparing calculated bolus users to manual bolus users, there was no difference in HbA1C improvement (P = .58).ConclusionWe found that CSII improves glucose control in patients with DM2 who have failed MDI despite a decrease in overall insulin requirements. This includes patients with severe insulin resistance using U-500 insulin. Use of frequent bolus adjustment incorporating carbohydrate counting and current glucose level does not appear to be required for this benefit. (Endocr Pract. 2013;19: 9-13)     

Glycemic Effects Of Sglt-2 Inhibitor Canagliflozin In Type 1 Diabetes Patients Using The Dexcom G4 Platinum Cgm

Objective: Limited information is available on chronic use of sodium glucose cotransporter 2 inhibitors in type 1 diabetes (T1D). We conducted a retrospective review of T1D patients on Dexcom G4Platinum continuous glucose monitors (DCGMs) >1 year (mean, 4.6 years) who were prescribed canagliflozin (CANA) 100 mg daily and had a baseline DCGM 30-day download prior to and a second download after at least 1 month (mean, 3.7 months) taking CANA 100 mg daily. The glycemic, weight, and systolic blood pressure (SBP) effects are reported.Methods: We identified 27 patients meeting the selection criteria: 14 men; 25 white; 22 on pump; average T1D duration, 34 years (range, 12 to 48 years); average hemoglobin A1C (A1C), 7.6% (range, 6.1 to 9.8%); 22 with baseline A1C 7.0% or higher. All patients had an estimated glomerular filtration rate (eGFR) at baseline of 60 mL/min/1.73 m² or higher and were normotensive or on stable therapy. On average, 29 days of CGM data was reviewed. Total daily insulin dose (TDD) was available in 21 patients. We identified 27 patients who were judged to be candidates for CANA but did not have any change in glycemic therapy other than insulin adjustment as controls.Results: CANA resulted in significant reductions in mean blood glucose, CGM standard deviation, time in hyperglycemia, A1C, weight, SBP, and TDD, with increased time in target, with minimal increase in hypoglycemia and no significant change in eGFR. Three females developed genital mycotic infections but continued therapy, 2 developed ketoacidosis from insulin interruption.Conclusion: CANA offers promise as adjunct therapy in T1D, though caution is advised.Abbreviations:A1C = hemoglobin A1CCANA = canagliflozinCGM = continuous glucose monitorCSII = continuous subcutaneous insulin infusionDCGM = Dexcom G4Platinum CGMDKA = diabetic ketoacidosisGMI = genital mycotic infectionMG = mean glucosePCGM = personal continuous glucose monitoringSBP = systolic blood pressureSGLT-2i = sodium-glucose cotransporter 2 inhibitorSH = severe hypoglycemiaT2D = type 2 diabetesT1D = type 1 diabetes     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Once-Daily Insulin Glargine Versus 6-Hour Sliding Scale Regular Insulin for Control of Hyperglycemia after a Bariatric Surgical Procedure: A Randomized Clinical Trial

ObjectiveTo determine whether once-daily insulin glargine could provide better glycemic control after an abdominal surgical procedure than the traditional use of sliding scale regular insulin (SSRI).MethodsBecause 20% to 30% of patients undergoing gastric bypass have a history of overt diabetes and another 5% to 10% are estimated to have impaired glucose tolerance, we chose to study these patients. We treated 81 patients with postoperative blood glucose levels of more than 144 mg/dL after a Roux-en-Y gastric bypass surgical procedure. They were randomized to receive either SSRI or insulin glargine either directly or after initial intravenous insulin infusion in the intensive care unit (ICU).ResultsOverall, the mean blood glucose level after SSRI therapy was 154 ± 33 mg/dL, and the mean blood glucose value after insulin glargine treatment was 134 ± 30 mg/dL (P < 0.01). The mean blood glucose level for patients first treated with intravenous insulin infusion in the ICU was 125 mg/dL, in comparison with 145 mg/dL in the non-ICU patients whose treatment began directly with 0.3 U/kg of insulin glargine. Of 926 blood glucose measurements, only 3 were less than 60 mg/dL.ConclusionIn this study, control of postoperative hyperglycemia was significantly better with use of insulin glargine in comparison with SSRI therapy, and hypo-glycemia was very infrequent. (Endocr Pract. 2007;13: 225-231)