Oral Hypoglycemic Use Research Articles

Associations of HIV and prevalent type 2 diabetes mellitus in the context of obesity in South Africa

Background It is unclear how rising obesity among people with HIV (PWH) impacts their risk of type 2 diabetes mellitus (diabetes). We examined associations between HIV, prevalent diabetes and adiposity among South African PWH and their peers without HIV (PWOH). Methods HIV status was ascertained by antibody testing. Diabetes was defined as current use of oral hypoglycemics, insulin, and/or HbA1c ≥6.5%. Adiposity was measured by body mass index (BMI), waist circumference and waist-to-height ratio. Their associations were examined using sex-stratified multivariable fractional polynomial generalized linear models, reporting adjusted prevalence and prevalence ratios (adjPR). Results The mean age among 1,254 PWH and 4,381 PWOH was 41 years (95%CI 28, 56). The prevalence of diabetes among males was similar between PWH [11.3% (7.1, 15.5)] and PWOH [9.8% (8.5, 11.1); p=0.740]. By contrast, diabetes prevalence was higher among female PWOH [15.7% (14.4, 17.0)] than female PWH [10.5 (8.3, 12.8)%; adjPR: 0.67 (0.51, 0.82); p<0.001]. This difference was accentuated with obesity but reversed with leanness. At BMI ≥25 kg/m2, female PWH had lower diabetes prevalence [adjPR: 0.58 (0.41, 0.76); p<0.001] than female PHIV. In contrast, at BMI <18 kg/m2, female PWH had higher prevalence [adjPR: 1.72 (−1.53, 4.96); p=0.756] than female PWOH. Conclusion We found sex-specific differences in the relationship between adiposity and diabetes prevalence by HIV serostatus in South Africa. Notably, females living with obesity and HIV had lower prevalence of diabetes than females living with obesity and without HIV, which may have particular implications for diabetes prevention programs in the region.

Insulin-like growth factor-1 and cognition in normoglycemia, prediabetes, and type 2 diabetes mellitus

BackgroundThe relationship between insulin-like growth factor-1 (IGF-1) and cognition has been studied in healthy individuals, but not extensively with regards to insulin resistance and type 2 diabetes mellitus (T2DM). In this retrospective observational study, we investigated relationships of IGF-1 with memory and executive function across people with normoglycemia, prediabetes, and T2DM. MethodsData from the Midlife in the United States (MIDUS) study were used. Episodic memory and executive function were assessed using the Brief Test of Adult Cognition by Telephone approximately 21.42 ± 12.10 months prior to measuring IGF-1 levels from a fasting blood sample. Normoglycemia was identified as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) ≤5.6%. Prediabetes was identified as those without a physician diagnosis of diabetes and HbA1c between 5.7%−6.4%. T2DM was identified as anyone with a physician diagnosis of diabetes, or HbA1c ≥6.5%, or anyone using an oral hypoglycemic medication. The associations were assessed using linear regressions controlling for age, sex, education, body mass index, C-reactive protein, HbA1c or homeostatic model of insulin resistance, MIDUS wave, exercise, smoking status, sleep quality, alcohol intake, oral hypoglycemic use, and insulin use. ResultsThe study included 1400 participants, which consisted of 583 normoglycemic (48.4% female, mean age 51.0 ± 12.2 years), 512 prediabetes (58.4% female, mean age 57.3 ± 11.8 years), and 305 T2DM participants (53.8% female, mean age 57.6 ± 11.5 years). Peripheral IGF-1 concentrations were lower (F2,1397 = 28.29, p < 0.001) in people with prediabetes or T2DM, vs. normoglycemia. Participants with prediabetes or T2DM had lower episodic memory (F2,1397 = 9.21, p < 0.001) and executive function (F2,1397 = 20.29, p < 0.001) composite z-scores than people with normoglycemia. Higher IGF-1 concentrations were associated with better executive performance in individuals with prediabetes (β = 0.115 [0.028, 0.202], p = 0.010), but not in individuals with normoglycemia or T2DM. An interaction between IGF-1 and sex in predicting executive function was observed in the prediabetes group (β = −0.344, p = 0.042), where the relationship was weaker in females (β = 0.106 [−0.012, 0.224], p = 0.077) than males (β = 0.251 [0.123, 0.380], p < 0.001). No associations were seen between IGF-1 and memory. ConclusionThe results suggest that peripheral IGF-1 concentrations may be related to executive function, and that the relationship may be sex-specific and dependent on diabetes status.

214: HYPOGLYCEMIA: COMMON BUT UNCOMMONLY IRREVERSIBLE

Introduction: Whipple’s Triad is comprised of symptomatic low blood glucose (< 55 mg/dL) and resolution of symptoms after correction of glucose level, indicating the presence of hypoglycemic disorder. Hypoglycemia is often easily reversed with standardized treatment, however; in few cases, hypoglycemia is refractory to standard treatment, requiring further investigation. Hypoglycemia can be associated with prolonged hospitalizations as well as higher morbidity and mortality. Description: 86-year-old white female was admitted to the intensive care unit (ICU) with sepsis. Patient presenting symptoms included: worsening of baseline confusion, generalized weakness, and diaphoresis. Patient arrived to ICU with tremors and a blood glucose level of 50mg/dL (74-99mg/dL). She had no insulin or oral glycemic agents prior to admission. The hypoglycemia protocol was initiated, which included dextrose containing fluids and glucagon. Octreotide and steroids were added, and dextrose fluid concentration increased due to persistent hypoglycemia. Her lack of response led to further evaluation. Differential diagnoses included: cortisol deficiency, insulinoma, insulin autoimmune syndrome and beta cell hypertrophy. Laboratory studies during hypoglycemic episode were obtained which revealed: random cortisol 13.2 mcg/dL, proinsulin greater than 700 pmol/L (3.6-22 pmol/L), insulin level 103 uIU/mL (2.6-24.9 uIU/mL), C-peptide 22.8 ng/mL (1.1-4.4 ng/mL), and insulin antibody (Ab) level zero. Absence of gastric bypass history made beta cell hypertrophy unlikely. Elevated proinsulin levels as well as an insulin and C-peptide ratio of less than one, both present in this patient, are highly suggestive of insulinoma in the absence of oral hypoglycemic use. No further investigation was pursued due to family wishes to focus on comfort care. Discussion: Hypoglycemia is prevalent in critical care. One should keep an open mind when investigating causes of hypoglycemia when standard treatment does not lead to resolution. A detailed history is important when hypoglycemia persists. Insulin, proinsulin, C-peptide levels, and appropriate imaging should be checked during hypoglycemic episode to determine correct diagnosis and management.

Antrum Preservation Versus Antrum Resection in Laparoscopic Sleeve Gastrectomy With Effects on Gastric Emptying, Body Mass Index, and Type II Diabetes Remission in Diabetic Patients With Body Mass Index 30–40 kg/m2: a Randomized Controlled Study

BackgroundLaparoscopic sleeve gastrectomy (LSG) is a widely performed procedure nowadays. There is a controversy on whether antrum resection (AR) or antrum preservation (AP) should be done and if this has an effect on BMI, gastric emptying, and associated medical conditions such as diabetes mellitus (DM).Study DesignThis randomized controlled trial included 56 patients in the AP group and 53 patients in the AR group with BMI 30–40 kg/m2. Weight, BMI, fasting and postprandial blood glucose (FBS and PPBS), HbA1C, oral hypoglycemic drug use, and % gastric emptying by gastric scintigraphy at 30, 60, 90, and 120 min were recorded preoperatively and postoperatively at 3, 6, and 12 months. Postoperative % of total weight loss (TWL) and symptoms of de novo GERD were observed at 3, 6, and 12 months.ResultsThe AR group had significantly lower BMI and HbA1C and higher %TWL than the AP group. There was a significant difference between the two groups regarding % of gastric emptying with the AP group showing higher values at 30, 60, 90, and 120 min. There were no significant differences regarding FBS, PPBS, and oral hypoglycemic use. The AR group had more incidence of GERD symptoms postoperatively yet with no significant difference.ConclusionLSG with antrum resection (2 cm from the pylorus) had significantly less postoperative BMI, higher %TWL, better control of type II DM, and more retention of gastric contents in patients with BMI 30–40 kg/m2 in comparison with LSG with antral preservation with non-significant increase in incidence of GERD symptoms.Graphical abstract

Remission of Type II Diabetes Mellitus 1-Year Postoperative Following One Anastomosis Gastric Bypass in Correlation with ABCD, DiaRem, and DRS Scores.

Diabetes mellitus (DM) is a debilitating chronic illness. Roux en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) present a potential solution to type II DM. Several scoring systems predict DM remission as ABCD score, DiaRem score, and diabetes remission score (DRS). This was a retrospective study that included 138 patients with DM and underwent OAGB. BMI, HbA1C, insulin, and oral hypoglycemics need were recorded pre- and postoperatively with calculation of ABCD, DiaRem, and DRS scores. Effects of OAGB on DM were observed and correlated with the scoring systems to detect their sensitivity and specificity. Age, preoperative, and postoperative BMI were 47.38 ± 7.632, 45.096 ± 4.465, and 31.173 ± 3.799 respectively. The preoperative and stimulated C-peptides were 3.357 ± 0.995 and 4.158 ± 0.897ng/ml respectively. The preoperative and postoperative HbA1C were 7.396 ± 0.743% and 6.564 ± 0.621% respectively. Patients with complete remission were 32 patients (23.2%) and with partial remission were 46 patients (33.3%) adding to 56.5% considered in remission. There was significant decrease of BMI, HbA1C, insulin, and oral hypoglycemic use postoperatively. Receiver operator characteristics (ROC) curve showed that ABCD, DiaRem, and DRS scores had AUC of 0.853 with cut-off > 5, 0.921 with cut-off ≤ 8, and 0.805 with cut-off ≤ 8 respectively. The DiaRem score had the highest AUC followed by ABCD score then DRS score. OAGB significantly reduced BMI and HbA1C values 1year postoperatively with 56.5% DM remission. DiaRem score had more remission predictive value following OAGB than ABCD and DRS scores especially when ≤ 8 with 90.6% sensitivity and 83% specificity.

1163 Development of a risk calculator for shoulder dystocia in patients with diabetes

To develop a multivariable risk calculator for shoulder dystocia (SD) in patients with diabetes (DM) in pregnancy using information available prior to delivery, including the Fetal Abdominal Adiposity Score (FAAS), a novel ultrasound-based metric 23,862 third trimester ultrasounds of singleton pregnancies delivered at a single center from 2007-2017 were used to develop normative data by gestational week for the FAAS, calculated as biparietal diameter minus abdominal diameter (abdominal circumference/pi). Vaginal deliveries of live, singleton, non-anomalous fetuses to patients with DM at the same center 2002-2013 were identified within an NIH-funded database of pregnancy and delivery information extracted by trained research nurses. The FAAS was calculated from the last ultrasound before delivery, and was used in a multivariable predictive model. Forward selection was employed, with internal validation via boot-strapping. The model was used to identify pregnancies within this cohort with SD risk of ≥20%. SD occurred in 33 of 757 pregnancies (4.4%). 26 candidate predictors were analyzed and 7 included in the final model: FAAS, diabetes type (type 1, type 2, gestational, or unknown), fetal sex, pre-pregnancy BMI, oral hypoglycemic use in pregnancy, dietary control of diabetes in pregnancy, and maternal race. The area under the curve (AUC) was 0.77 (95% CI 0.69-0.86), superior to FAAS alone (AUC 0.60, CI 0.53-0.68, p= <0.001) or macrosomia alone (AUC 0.52, CI 0.48-0.56, p= <0.001). FAAS alone was superior to macrosomia alone (p=0.04). Random resampling for 1000 replications confirmed these results (AUC 0.77, CI 0.71-0.90). 19 pregnancies with SD risk of ≥20% were identified, none with macrosomia. SD occurred in 9 of of these (47%) vs 24 of 738 (3.25%) with a predicted SD risk of <20% (p= <0.001). A multivariable model including FAAS was superior to macrosomia and FAAS alone for prediction of SD in diabetic patients, identifying non-macrosomic fetuses at risk. If validated prospectively, this model can aid decision-making regarding mode of delivery in diabetic patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Association of Urinary Polycyclic Aromatic Hydrocarbons and Diabetes in Korean Adults: Data from the Korean National Environmental Health Survey Cycle 2 (2012-2014).

PurposeTo investigate the associations between the urinary levels of polycyclic aromatic hydrocarbons (PAHs) and diabetes mellitus in Korean adults.Materials and MethodsWe examined the data of 6478 participants aged ≥19 years from the Korean National Environmental Health Survey (KoNEHS) cycle 2 (2012–2014). The urinary levels of 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenathrene (1-OHPhe), and 2-hydroxyfluorene (2-OHFlu) were measured by gas chromatography-mass spectrometry. Diabetes mellitus was defined as a self-report of physician-diagnosed diabetes mellitus or the use of oral hypoglycemics or insulin. Analyses were adjusted for sex, age, body mass index, household income, alcohol consumption, physical activity, urinary creatinine and cotinine, menopausal status, and quartiles of all other PAHs.ResultsThe prevalence of diabetes was 6.5% in the study population. In men, the geometric means of the 2-NAP and 2-OHFlu levels were higher in participants with diabetes mellitus than in those without diabetes mellitus [4.11 vs 3.26 μg/L (P <0.05) and 0.45 vs 0.40 μg/L (P <0.05), respectively]. In women, the geometric mean of 2-NAP levels was also higher in participants with diabetes mellitus than in those without diabetes mellitus (1.81 vs 0.56 μg/L, P <0.05), but there were no significant differences in geometric means for other PAHs. A higher odds ratio (OR) of diabetes was found in participants with the highest quartiles of urinary 2-NAP [OR 1.83, 95% confidence interval (CI) 1.29–2.60] and 2-OHFlu (OR 1.81, 95% CI 1.10–2.98) than in those with the lowest quartiles.ConclusionThe urinary 2-NAP and 2-OHFlu levels were associated with diabetes mellitus in Korean adults. Further studies are needed to determine a potential causal relationship between PAH exposure and diabetes mellitus and its underlying mechanism.

382: Concomitant insulin and oral hypoglycemic use predicts the diagnosis of type II diabetes

Women with gestational diabetes (GDM) often remain diabetic postpartum (PP) but high rates of noncompliance frequently lead to under diagnosis. We sought to understand what antepartum factors were associated with persistent diabetes to inform more focused follow-up. This was a planned secondary analysis of a prospective cohort of women with GDM undergoing 75-gram oral glucose tolerance test (OGTT) at 6 weeks PP. A diagnosis of Type II DM was made if glucose level was >199 mg/dL. Bivariate analysis was initially performed to select variables for multivariable analysis. 446 included women, 157 (35%) completed an OGTT screening and 15.9% had persistent diabetes. Age, race, prior history of GDM and BMI were similar between the two groups (p >0.05). Neonates of women tended to be lighter amongst women with persistent diabetes (p=0.04) but this trend did not persist in multivariable analysis. Women who required both hypoglycemic medication and insulin to control their diabetes were at increased odds of Type II DM by more than 4 times (OR 4.3, 95%CI 1.4-12., p< 0.008). Women with concomitant insulin and oral hypoglycemic use are at a significantly higher risk of screening positive for type II DM in the PP period. With the reported low rates of compliance and the high rate of Type II DM in this cohort, these women should be strongly counseled about the short term and long-term potential risks of missing their postpartum screening.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Rates of Overtreatment and Deintensification of Antidiabetic and Antihypertensive Medications in Patients with Diabetes Mellitus

Background: Targeting better HbA1c and blood pressure (BP) goals may endanger older adults with type 2 diabetes mellitus (T2DM) for a number of risks. Overtreatment of T2DM and hypertension (HTN) is a trending issue but awareness and attitudes of physicians need to be explored. Objective: To assess the rates and predictors of overtreatment and undertreatment of glycemia and blood pressure in older adults with T2DM. Treatment deintensification or intensification by the physicians were also investigated. Method: Data from older adults (≥65 years) enrolled in a large nationwide T2DM survey in 2017 across Turkey were analyzed. Overtreatment was defined as HbA1c &amp;lt;6.5% plus use of ≥2 oral hypoglycemics or insulin, and systolic BP &amp;lt;120 mmHg or diastolic BP &amp;lt;65 mmHg plus use of ≥2 drugs). Undertreatment was defined as HbA1c &amp;gt;9% at all, and SBP &amp;gt;140 mmHg or DBP &amp;gt;90 mmHg plus use of &amp;lt;3 drugs. Deintensification or intensification rates were calculated according to treatment modification by the physicians. Results: A total of 1276 patients were included. The overtreatment rates for glycemia and BP were 9.8% and 5.9%, whereas undertreatment rates were 14.2% and 17.7%, respectively. In the adjusted model, use of oral hypoglycemics only (OR:3.1, 95% CI:1.9-5.3) and follow-up at a private clinic (OR:2.2, 95% CI:1.2-3.9) were the predictors of glycemia overtreatment. Presence of microvascular complications (OR:2.0, 95% CI:1.1-3.5) was the only predictor of BP overtreatment. The deintensification and intensification rates for glycemia were 25% and 75.7% respectively, and for the BP 10.9% and 9.0% respectively. Conclusion: The overtreatment rates of diabetes and BP in Turkish older adults with T2DM were consistent with the previous studies, while the undertreatment rates were much higher. Doctors seem to feel more comfortable to intensify glycemic management and largely ignore BP control. The results warrant enforced measures to improve care of older adults with T2DM. Disclosure A. Sonmez: None. I. Tasci: None. I. Demirci: None. C. Haymana: None. C. Barcin: None. H. Aydin: None. S. Cetinkalp: None. F. Yener Ozturk: None. K. Gul: None. T. Sabuncu: None. I. Satman: None. F. Bayram: None.

Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies.

T2D is independently associated with increased risk for HCC in two prospective cohorts of U.S. men and women. This risk is enhanced with prolonged diabetes duration and with comorbid metabolic conditions, suggesting the importance of insulin resistance in the pathogenesis of HCC. (Hepatology 2018;67:1797-1806).

Effect of systemic insulin treatment on diabetic wound healing.

This study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow-up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1-90.1 years) and 58 cases (68.2%) were males. Twenty-four cases reached a complete healing (healing rate: 22.4%). The median follow-up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7-21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random-effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x-ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates.

A Risk Prediction Model for Sporadic CRC Based on Routine Lab Results.

Current risk scores for colorectal cancer (CRC) are based on demographic and behavioral factors and have limited predictive values. To develop a novel risk prediction model for sporadic CRC using clinical and laboratory data in electronic medical records. We conducted a nested case-control study in a UK primary care database. Cases included those with a diagnostic code of CRC, aged 50-85. Each case was matched with four controls using incidence density sampling. CRC predictors were examined using univariate conditional logistic regression. Variables with p value <0.25 in the univariate analysis were further evaluated in multivariate models using backward elimination. Discrimination was assessed using receiver operating curve. Calibration was evaluated using the McFadden's R2. Net reclassification index (NRI) associated with incorporation of laboratory results was calculated. Results were internally validated. A model similar to existing CRC prediction models which included age, sex, height, obesity, ever smoking, alcohol dependence, and previous screening colonoscopy had an AUC of 0.58 (0.57-0.59) with poor goodness of fit. A laboratory-based model including hematocrit, MCV, lymphocytes, and neutrophil-lymphocyte ratio (NLR) had an AUC of 0.76 (0.76-0.77) and a McFadden's R2 of 0.21 with a NRI of 47.6%. A combined model including sex, hemoglobin, MCV, white blood cells, platelets, NLR, and oral hypoglycemic use had an AUC of 0.80 (0.79-0.81) with a McFadden's R2 of 0.27 and a NRI of 60.7%. Similar results were shown in an internal validation set. A laboratory-based risk model had good predictive power for sporadic CRC risk.

Outcomes After Simultaneous Pancreas and Kidney Transplantation and the Discriminative Ability of the C-peptide Measurement Pretransplant Among Type 1 and Type 2 Diabetes Mellitus

Background Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease. Methods To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m 2 and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT. Results Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM. Conclusion SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.

Long-term Safety of Testosterone and Growth Hormone Supplementation: A Retrospective Study of Metabolic, Cardiovascular, and Oncologic Outcomes

BackgroundClinical research into the effects of hormonal supplementation has tended to focus on beneficial changes in anthropometric measures. There are fewer data on long-term safety with extended hormonal supplementation.MethodsAs part of a retrospective database survey, clinical outcomes were tabulated among patients who received at least 1 year of testosterone and/or growth hormone (GH) supplementation. In patients who were treated for at least 2 years, changes in markers of glucose and lipid metabolism were analyzed with and without concomitant use of oral hypoglycemics and statins.ResultsIn 263 patients (mean age 56) treated for at least 2 years, the only statistically significant effect on markers of glucose metabolism was an increase in glycated hemoglobin (still within normal limits) in patients receiving GH alone or in combination with testosterone but without oral hypoglycemics; with or without hypoglycemics, insulin levels showed no significant change. The only significant effects on markers of lipid metabolism were decreases in total cholesterol and low-density lipoprotein (LDL) in patients receiving combined testosterone and GH without statins. Decreases in LDL were significant in both the statin and non-statin groups; decreases in triglycerides were significant only in the statin group. In 531 patients treated for at least 1 year (mean age 54), the overall incidence of adverse clinical outcomes (prostate disease, diabetes, cardiovascular disease, cancer) was 1.3%.ConclusionsIn this retrospective survey, extended testosterone and/or GH supplementation did not adversely affect metabolic markers or clinical outcomes.KeywordsSafety; Testosterone; Growth hormone; Supplementation

Oral Hypoglycemic Use and the SANDS Trial—Reply

Oral Hypoglycemic Use and the SANDS Trial—Reply

Oral Hypoglycemic Use and the SANDS Trial

Oral Hypoglycemic Use and the SANDS Trial

Is routine electrolyte testing necessary for diabetic patients who present to the emergency department with moderate hyperglycemia?

No consensus standard is established for the workup of diabetic patients with moderate hyperglycemia [fingerstick glucose of 11.00-33.00 mmol/l (200-600 mg/dl)]. We measured the incidence of serious electrolyte abnormalities in patients with moderate hyperglycemia and attempted to identify a subset of these patients who can safely forego routine electrolyte testing. Prospective cohort study in two affiliated emergency departments. Moderate hyperglycemia. new onset diabetes or renal failure. The composite outcome was defined as an abnormal potassium K >5.00 or <3.50 mmol/l or diabetic ketoacidosis. Univariate analyses were performed using t-test and Fisher's exact test (alpha=0.05, two-tails). Logistic regression models were generated to identify variables that could predict the composite outcome. Three hundred and ninety-nine adults were enrolled (294 type II, 38% men). Mean age was 59+/-15 (20-97 years) years. The incidence of the composite outcome was 22% (95% confidence interval, 17.8-26.0%, n=86). The univariate analysis identified potassium-altering medications and insulin use as risk factors for the composite outcome. Logistic regression analysis identified potassium-altering medications as an increased risk (relative risk: 1.64, 95% confidence interval, 1.14-2.37) and use of oral hypoglycemics as a decreased risk (relative risk: 0.62, 95% confidence interval, 0.43-0.90) of the composite outcome. Cross-validation of the model demonstrated poor sensitivity (76%) and even worse accuracy (51%). We failed to identify any subgroup of patients with moderate hyperglycemia who can be safely excluded from routine electrolyte testing. We recommend routine electrolyte testing for all moderate hyperglycemia patients in the emergency department.

Effect of Increased Cost-Sharing on Oral Hypoglycemic Use in Five Managed Care Organizations

For patients with a chronic disease, increased cost-sharing for medications may lead to unintended consequences, including reduced use of medications essential for control of their disease. The objective of this study was to estimate the effects of small ($1-6 per 30-day supply), moderate ($7-10), and large (>$10) increases in medication cost-sharing on 12-month trends in oral hypoglycemic (OH) use among adults with type 2 diabetes. We conducted a quasiexperimental study using a time series with comparison group design. Data were obtained from computerized membership, benefit, and pharmacy dispensing data of 5 managed care organizations (MCOs). A total of 13,110 12-month episodes of OH use and a medication cost-sharing increase ("intervention") were matched with 13,110 that had no increase. The dependent variable was OH average daily dose (ADD) standardized to each episode's mean OH ADD in the 6-month preintervention period. The principal independent variable was change in cost per 30-day OH supply between the 6-month pre- and postintervention periods. Effects of changes in cost-sharing on OH ADD were estimated using segmented time series regression. Episodes with >$10 increase in cost-sharing had significantly (alpha=0.05) decreased OH ADD in the postintervention period. At 6 months after this increase, OH ADD had decreased by 18.5% from that predicted from the preintervention trend. Episodes with a $1 to $10 increase in cost-sharing and those with no increase in cost-sharing had significant linear increases in OH use over the 12-month period. Large increases in medication cost-sharing were associated with immediate and persistent reductions in OH use. Small and moderate increases had little effect on OH use in the 6-month period after the increase.

African-American ethnicity is no longer a risk factor for early adverse outcomes in simultaneous kidney–pancreas transplantation with contemporary immunosuppression

The influence of ethnicity on the outcome of simultaneous kidney–pancreas transplantation (SKPT) is controversial. The aim of this study was to determine the impact of ethnicity on the major endpoints of a prospective, multicenter, randomized trial of two dosing regimens of daclizumab compared to no-antibody induction in SKPT. A total of 297 patients were randomized into three groups: daclizumab 1 mg/kg/dose every 14 days for five doses (group I, n = 107); daclizumab 2 mg/kg/dose every 14 days for two doses (group II, n = 112), and no-antibody induction (group III, n = 78). All patients received tacrolimus, mycophenolate mofetil, and steroids for maintenance immunosuppression. Thirty-seven patients (12.5%) were African-American (AA) and 260 were non–African-American (NAA). Demographics and transplant characteristics were comparable between AA and NAA patients. At 1 year, no differences were seen in patient survival (97% AA, 96% NAA), kidney graft survival (94% AA, 93% NAA), and pancreas graft survival (84% AA, 85% NAA). Rejection rate and incidence of adverse events were similar between AA and NAA subjects. Kidney graft function was comparable between AA and NAA patients at 1 year; however, mean HgbA1C was higher, C-peptide was lower, and oral hypoglycemic use was more common in AA subjects. Thus, in this prospective multicenter study, AA ethnicity was not associated with an increased risk of early adverse outcomes in SKPT. Follow-up will be required to determine whether long-term outcomes remain equivalent, particularly with regard to pancreas graft function.

Incidence of diabetic retinopathy in the Barbados Eye Studies

Purpose To examine the 4-year incidence and risk factors for diabetic retinopathy (DR) among black participants with diabetes in the Barbados Eye Studies (BES). Design Population-based incidence study. Setting and participants Four hundred ten persons with diabetes mellitus (DM) from the BES cohort, which was based on a simple random sample of Barbadians, 40 to 84 years of age at baseline. Main outcome measures Development of DR, assessed by independent gradings of 30° color stereo fundus photographs of the disc and macula. Associations were evaluated by logistic regression analyses. Results After 4 years, DR developed in 92 of 306 (30.1%; 95% confidence interval, 25.0%, 35.5%) persons unaffected at baseline. The incidence of DR was 31.9% in those with known DM at baseline and 20.9% in newly diagnosed DM. Clinically significant macular edema developed in 16 (4.5%) of 353 individuals at risk. Seven (6.9%) of the 101 persons with minimum or moderate DR at baseline progressed to proliferative DR. Age-specific incidence declined from 36.2% at age 40 to 49 years to 28.8% and 24.2% over the subsequent two decades, increasing to 38.2% among those ≥70 years. Risk factors for DR were increased systolic blood pressure (relative risk [RR], 1.16 [1.03, 1.31]/10 mmHg increase); use of oral hypoglycemics (RR, 2.4 [1.3, 4.2]); and use of insulin (RR, 6.1 [1.7, 22.1]) (vs. no treatment or diet only); and elevated glycated hemoglobin (GHb; RR, 6.4 [2.5, 16.0]); GHb >11.5% vs. GHb ≤8%). Conclusions High rates of incident DR were evident in the black BES population, also known to have high rates of DM. Prevention of visual loss caused by DR in this population has high priority, including optimal glycemic and blood pressure control.