Opportunistic Screening For Diabetes And Prediabetes Using Hemoglobin A1C In An Urban Primary Care Setting

Objective: In 2010, the American Diabetes Association (ADA) endorsed hemoglobin A1c (HbA1c) as 1 of 3 tests for diabetes and prediabetes screening. We describe the use of HbA1c testing for screening during routine visits in primary care clinics of an urban health care system in the U.S.Methods: In 2013 to 2014, retrospective analyses of deidentified electronic health records over a 2-year period, January 2010 to December 2011, for academic private practices (clinic group 1) and federally-qualified Community Health Centers (clinic group 2) identified 11,885 adults without prior diabetes or recent HbA1c testing. We estimated the proportion of patients eligible for screening according to ADA and U.S. Preventative Services Task Force (USPSTF) guidelines and calculated the potential yield of previously undiagnosed diabetes or prediabetes among those who received at least 1 HbA1c test.Results: Overall, 3,316 and 5,613 patients of clinic groups 1 and 2 (75.2% of each) were eligible for screening by ADA guidelines, while only 1,764 (39.9%) of clinic group 1 and 3,799 (50.9%) of clinic group 2 were eligible by USPSTF guidelines. In those eligible by either guideline, 731 (21.4%) patients of clinic group 1 and 1,293 (21.5%) of clinic group 2 received HbA1c testing; among these, in 71 (9.7%) and 121 (9.4%) patients from clinic groups 1 and 2, respectively, HbA1c results were in the diabetes range, and in 330 (45.2%) and 733 (56.7%), results were in the prediabetes range.Conclusion: In urban primary care settings, appropriate HbA1c testing could result in the detection of a substantial number of previously undiagnosed diabetes and prediabetes cases needing treatment.Abbreviations:ADA = American Diabetes AssociationBMI = body mass indexCI = confidence intervalEHR = electronic health recordHbA1c = hemoglobin A1cHTN = hypertensionICD = International Classification of DiseasesIFCC = International Federation of Clinical ChemistryOGTT = oral glucose tolerance testUSPSTF = U.S. Preventative Services Task Force     

Relationship Between Glycated Hemoglobin and Circulating 25-Hydroxyvitamin D Concentration In African American And Caucasian American Men

ObjectiveTo examine whether (1) serum 25-hydroxy- vitamin D level (25[OH]D) is a risk factor for hyperglycemia, as assessed by glycated hemoglobin (HbA1c), in African American men (AAM) and (2) 25(OH)D is a predictor of HbA1c in AAM and Caucasian American men (CAM).MethodsWe prospectively assessed 25(OH)D and HbA1c in 1,074 men, outpatients with and without diabetes, at an urban Veteran Administration Medical Center (66.8% AAM, 26.4% CAM, 6% Hispanic, 0.4% Asian, and 0.4% Native American men). Multivariate regression analyzed the determinants of HbA1c after accounting for potential confounders.ResultsWe found high prevalence of low (< 30 ng/mL) 25(OH)D (81%) and elevated (≥5.7%) HbAlc (53.5%). The 25(OH)D was inversely associated with HbA1c in all men (r = −0.12, P<.001), in AAM (r = −0.11, P = .003), and in CAM (r = −0.15, P = .01). In the entire group the independent determinants of HbA1c included body mass index (BMI), age, 25(OH)D levels, systolic blood pressure (BP), triglycerides, high-density lipoprotein (HDL), and current alcohol use (P<.0001, .013, .009, .01, .008, .034, and .048, respectively) while glomerular filtration rate (GFR) and marital status showed borderline significance (P = .08 and .09, respectively). In AAM these determinants included BMI, 25(OH)D levels, systolic BP, and current alcohol use (P<.0001, .01, .02, and .03, respectively), while age had borderline significance (P = .06). In CAM, these included BMI, age, and triglycerides (P = .01, .03, and .004, respectively) but not 25(OH)D levels (P = .50).ConclusionCirculating low 25(OH)D is a risk factor for hyperglycemia, as assessed by HbA1c, in AAM. The 25(OH)D level is an independent determinant of HbA1c in AAM, but not in CAM, including men with and without diabetes. (Endocr Pract. 2013;19:73-80)     

Serum Levels of Carcinoembryonic Antigen in Patients with Type 2 Diabetes

Objective: To investigate whether serum carcinoembryonic antigen (CEA) levels are associated with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c).Methods: A comparative, cross-sectional, observational study was conducted at Jordan University Hospital, Amman, Jordan, on 282 adult subjects from March 2012 to June 2015. Subjects were classified into 2 groups: T2DM subjects (n = 168) and a healthy comparison group (n = 114). Subjects with any condition known to be associated with elevated CEA levels were excluded. HbA1c and serum CEA levels were measured, and body mass index (BMI) was determined.Results: Subjects with T2DM had significantly higher mean serum CEA than controls (2.4 ± 1.5 vs. 1.5 ± 1.2 ng/mL, P<.0001). Sex did not correlate with CEA levels, while age (Spearman's rho [ρ] = 0.18, P =.002) and HbA1c (ρ = 0.56, P<.0001) did; however, age no longer correlated after correcting for diabetic status. HbA1c was the only variable shown to correlate with CEA in a stepwise linear regression (r = 0.37, P<.001).Conclusion: We observed a statistically significant association between elevated CEA and T2DM, despite average CEA values for both groups being within the reference range. In addition, serum CEA levels correlated positively with HbA1c values.Abbreviations:ADA = American Diabetes AssociationBMI = body mass indexCA 19-9 = carbohydrate antigen 19-9CEA = carcinoembryonic antigenCRP = C-reactive proteinDM = diabetes mellitusHbA1c = glycated hemoglobinJUH = Jordan University HospitalT2DM = type 2 diabetes mellitusρ = Spearman's correlation coefficient     

Performance of A1C Versus Ogtt for the Diagnosis of Prediabetes in a Community-Based Screening

Objective: Reliable identification of individuals at risk for developing diabetes is critical to instituting preventative strategies. Studies suggest that the accuracy of using hemoglobin A1c as a sole diagnostic criterion for diabetes may be variable across different ethnic groups. We postulate that there will be lack of concordance between A1c and the oral glucose tolerance test (OGTT) for diagnosing prediabetes across Hispanic and non-Hispanic white (NHW) populations.Methods: A total of 218 asymptomatic adults at risk for type 2 diabetes (T2D) were assessed with A1c and OGTT for the diagnosis of prediabetes. Glucose homeostasis status was assigned as no diabetes (A1c <5.7% [39 mmol/mol]), prediabetes (A1c 5.7 to 6.4% [46 mmol/mol]), and T2D (A1c >6.4% [46 mmol/mol]). Inclusion criteria were age >18 years and at least one of the following: a family history of diabetes, a history of gestational diabetes, Hispanic ethnicity, non-Caucasian race, or obesity. Subjects received a fasting 75-g OGTT and A1c on the same day. Bowker's test of symmetry was employed to determine agreement between the tests.Results: Data from 99 Hispanic patients and 79 NHW patients were analyzed. There was no concordance between A1c and OGTT for Hispanic (P =.002) or NHW individuals (P =.003) with prediabetes.Conclusion: A1c is discordant with OGTT among Hispanic and NHW subjects for the diagnosis of prediabetes. Sole use of A1c to designate glycemic status will result in a greater prevalence of prediabetes among Hispanic and NHW New Mexicans.Abbreviations:A1c = hemoglobin A1cBMI = body mass indexCDC = Centers for Disease ControlCI = confidence intervalFPG = fasting plasma glucoseNHW = non-Hispanic whiteOGTT = oral glucose tolerance testT2D = type 2 diabetesWHO = World Health Organization     

The Association of Decreased Serum Gdnf Level with Hyperglycemia and Depression in Type 2 Diabetes Mellitus

Objective: Comorbidity of diabetes and depression is a critical problem. Decreased glial-derived neurotrophic factor (GDNF) has been demonstrated in depression, but no evidence of a relationship between GDNF and diabetes has been shown. The present studies were designed to investigate the relationship between GDNF and metabolism.Methods: In Study 1, we performed a case-control study in which subjects with type 2 diabetes mellitus (T2DM), prediabetes (p-DM), and normal glucose tolerance (NGT) were included. In Study 2, we performed a cross-sectional study in 296 patients having pre-existing diabetes in whom the levels of serum GDNF, blood glucose, blood lipids, blood pressure, body mass index, scores from the Patient Health Questionnaire (PHQ-9), the EuroQol-5 scale, and the diabetes distress scale were measured, as well as single-nucleotide polymorphisms of GDNF including rs884344, rs3812047, and rs2075680.Results: In Study 1, serum GDNF concentration was significantly lower in the T2DM group than in the NGT group (NGT: 11.706 ± 3.918 pg/mL; p-DM: 10.736 ± 3.722 pg/mL; type 2 diabetes mellitus &lsqb;T2DM group]: 9.884 ± 2.804 pg/mL, P = .008). In Study 2, significantly decreased serum GDNF levels were observed in subjects with poor glycemic control or depression (glycated hemoglobin &lsqb;HbA1c] <7.0% without depression: 11.524 ± 2.903 pg/mL; HbA1c ≥7.0% without depression: 10.625 ± 2.577 pg/mL; HbA1c <7.0% with depression: 10.355 ± 2.432 pg/mL; HbA1c ≥7.0% with depression: 8.824 ± 2.102 pg/mL, P = .008). Double-factor variance analysis showed that glycemic control and depression were independent factors for the GDNF level. Moreover, the serum GDNF level was significantly inversely associated with the fasting plasma glucose, 2 hours postprandial plasma glucose, HbA1c, and PHQ-9 score.Conclusion: Glycemic dysregulation was an independent factor for the GDNF level. These findings suggest that GDNF level might be involved in the pathophysiology of T2DM and depression through various pathways.Abbreviations: BP = blood pressure; CHO = cholesterol; DDS = diabetes distress scale; DM = diabetes mellitus; EQ-5D = the health-related dimensions of the EuroQol-5 scale; FPG = fasting plasma glucose; GDNF = glial-derived neurotrophic factor; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NGT = normal glucose tolerance; PHQ-9 = Patient Health Questionnaire; p-DM = prediabetes; PPG = postprandial plasma glucose; SNP = single-nucleotide polymorphism; T2DM = type 2 diabetes mellitus; TG = triglyceride     

Impact of Family History of Diabetes on Diabetes Control and Complications

Objective: Our aim was to assess the impact of parental and sibling history of type 2 diabetes (T2D) on patient characteristics, glycemic control, and T2D complications.Methods: This cross-sectional study included adults with T2D. Type 1 diabetes and gestational diabetes patients were excluded. The laboratory data were retrieved from the patients' electronic files, and baseline measurements were obtained by the researchers.Results: The study included a total of 511 T2D patients, with a mean age of 60.1 ± 10.9 years and mean hemoglobin A1c of 8.94 ± 2.1% (74.2 ± 22.9 mmol/mol). Of these patients, 54% were male and 49.7% had a parental history of T2D. The patients with parental history of T2D were diagnosed at a younger age and had a higher body mass index (BMI) (P =.035) and higher waist circumference (WC) (P =.013) than those T2D patients with no parental history. Approximately 60% of the participants had siblings with a history of T2D, and in comparison with those with no sibling history, they had higher prevalence of cerebrovascular accidents (P =.02).Conclusion: Having a parental history of T2D is significantly associated with diagnosis at a younger age and a higher BMI and WC. Having a sibling history of T2D is significantly associated with worse cerebrovascular outcome.Abbreviations: ACR = albumin to creatinine ratio; BMI = body mass index; DBP = diastolic blood pressure; DM = diabetes mellitus; FBG = fasting blood glucose; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; LDL = low-density lipoprotein; SBP = systolic blood pressure; T2D = type 2 diabetes; TG = triglyceride; WC = waist circumference     

Effect of Gluten-FREE Diet on Metabolic Control and Anthropometric Parameters in Type 1 Diabetes with Subclinical Celiac Disease: A Randomized Controlled Trial

Objective: It is unclear whether the institution of gluten-free diet (GFD) is beneficial in patients with type 1 diabetes (T1DM) and subclinical celiac disease (CD). Our primary objective was to evaluate the effect of GFD on the frequency of hypoglycemia, in patients with T1DM and subclinical CD. Our secondary objective was to investigate the effect of GFD on height, weight, glycosylated hemoglobin (HbA1c), insulin dose requirement, and bone mineral homeostasis.Methods: We carried out a prospective open label randomized controlled trial (RCT). Patients with T1DM and subclinical CD were randomized to receive GFD or a normal diet for 1 year. The primary outcome was the frequency of hypoglycemic episodes (blood glucose <70 mg/dL) measured by self-monitoring of blood glucose (SMBG) at the sixth month of the study in the 2 groups.Results: Screening for CD was carried out in 320 T1DM patients. Thirty eligible patients were randomized to receive GFD (n = 15) or a normal diet (n = 15). The mean number of hypoglycemic episodes/month recorded by SMBG and the mean time spent in hypoglycemia measured by CGM (minutes) in the GFD group versus the non-GFD group at six months was 2.3 minutes versus 3.4 minutes (P = .5) and 124.1 minutes versus 356.9 minutes (P = .1), respectively. The mean number of hypoglycemic episodes/month significantly declined in the GFD group (3.5 episodes at baseline versus 2.3 episodes at the sixth month; P = .03). The mean HbA1c declined by 0.73% in the GFD group and rose by 0.99% in non-GFD group at study completion.Conclusion: This is the first RCT to assess the effect of GFD in T1DM and subclinical CD. A trend towards a decrease in hypoglycemic episodes and better glycemic control was seen in patients receiving GFD.Abbreviations: BMC = bone mineral content; BMI = body mass index; CD = celiac disease; CGM = continuous glucose monitoring; GFD = gluten-free diet; Hb = hemoglobin; HbA1c = glycosylated hemoglobin; iPTH = intact parathyroid hormone; RCT = randomized controlled trial; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus; tTG-IgA = tissue transglutaminase immunoglobulin A     

Clinical Recognition and Management of Patients with Prediabetes

Objective: Early identification and management of prediabetes is critical to prevent progression to diabetes. We aimed to assess whether prediabetes is appropriately recognized and managed among patients with impaired fasting glucose (IFG).Methods: We carried out an observational study of Olmsted County residents evaluated at the Mayo Clinic between 1999–2017. We randomly selected 108 subjects with biochemical criteria of IFG and 105 normoglycemic subjects. We reviewed their health records at baseline (1999–2004) and during follow up (2005–2017) collecting demographic and clinical data including vitals, diagnoses, laboratory, and medications associated with cardiovascular comorbidities. The main outcome was documentation of any recognition of prediabetes and management recommendations (lifestyle changes and/or medications).Results: At baseline (1999–2004), 26.85% (29/108) of subjects with IFG were recognized as having prediabetes, and of these 75.86% (22/29) received management recommendations with 6.9% (2/29) getting metformin. During follow-up (2005–2017), 26.67% (28/105) of initial cohort of normoglycemic subjects developed incident IFG and of these, 85.71% (24/28) were recognized as having prediabetes, and 58.33% (14/24) received management recommendations. During the entire study period, 62.50% (85/136) were recognized as having prediabetes of which 75.29% (64/85) had documented management recommendations. High body mass index (BMI) (≥35) was associated with increased recognition (odds ratio &lsqb;OR] 3.66; confidence interval &lsqb;CI] 1.065, 12.500; P = .0395), and normal BMI (<25) was associated with a lack of recognition (OR 0.146; CI 0.189, 0.966; P = .0413).Conclusion: Despite evidence supporting the efficacy of lifestyle changes and medications in managing prediabetes, this condition is not fully recognized in routine clinical practice. Increased awareness of diagnostic criteria and appropriate management are essential to enhance diabetes prevention.Abbreviations: BMI = body mass index; CI = confidence interval; EHR = electronic health records; FBG = fasting blood glucose; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; OR = odds ratio     

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study

Objective: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects.Methods: Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels.Results: In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group.Conclusion: Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.Abbreviations: AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference     

The Efficacy and Safety of Co-Administration of Sitagliptin With Metformin in Patients With Type 2 Diabetes at Hospital Discharge

Objective: Few randomized controlled trials have focused on the optimal management of patients with type 2 diabetes (T2D) during the transition from the inpatient to outpatient setting. This multicenter open-label study explored a discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in general medicine and surgery patients with T2D.Methods: Patients with HbA1c ≤7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53–75 mmol/mol) and those >9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge.Results: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 ± 2.3% and decreased to 7.30 ± 1.5% and 7.30 ± 1.7% at 3 and 6 months (P<.001). Patients with HbA1c <7% went from 6.3 ± 0.5% to 6.3 ± 0.80% and 6.2 ± 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction from 8.0 ± 0.6% to 7.3 ± 1.1% and 7.3 ± 1.3%, and those with HbA1c >9% from 11.3 ± 1.7% to 8.0 ± 1.8% and 8.0 ± 2.0% at 3 and 6 months after discharge (both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in 4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose <40 mg/dL was reported in <1% in all groups.Conclusion: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D.Abbreviations: BG = blood glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes     

Gender differences in adiponectin and low-grade inflammation among individuals with normal glucose tolerance,prediabetes, and type 2 diabetes

Background: Women with prediabetes and type 2 diabetes mellitus have a higher relative risk of cardiovascular disease than do men. The reason for this is unknown.Objective: We studied the gender differences in adiponectin and in low-grade inflammation, measured by high-sensitivity C-reactive protein (hs-CRP) and interleukin-1 receptor antagonist (IL-1RA), in individuals with normal glucose tolerance, prediabetes, and type 2 diabetes.Methods: In this population-based, cross-sectional study, all individuals born in 1942, 1947, 1952, 1957, and 1962 in Pieksämäki, East Finland, were recruited for participation. A 75-g oral glucose tolerance test and lipid panel were performed, and concentrations of adiponectin, hs-CRP, and IL-1RA were measured. The World Health Organization diagnostic criteria for diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were used. Statistical comparisons between men and women were performed by a bootstrap-type ANCOVA.Results: The eligible population included 1294 middle-aged individuals, and of these, 904 (406 men and 498 women) had complete data and were included in the analyses. Absolute adiponectin concentrations were significantly higher in women at all levels of glucose tolerance (normal, prediabetes, and type 2 diabetes), but the gender ratio (women to men) for adiponectin concentrations decreased linearly (P = 0.011) from normal glucose tolerance (1.61; 95% CI, 1.48–1.75) to prediabetes (1.57; 95% CI, 1.36–1.83) and diabetes (1.16; 95% CI, 0.87–1.53). Among participants with normal glucose tolerance, no significant difference was found between the sexes in hs-CRP or IL-1RA. Among patients with prediabetes or diabetes, women had significantly higher concentrations than did men for hs-CRP (for prediabetes, 2.0 vs 1.5 mg/L; ratio, 1.39; 95% CI, 1.04–1.85) and IL-1RA (for prediabetes, 255 vs 178 pg/mL; ratio, 1.43; 95% CI, 1.121.83). The gender ratios (women to men) increased linearly from normal glucose tolerance to prediabetes and type 2 diabetes for both hs-CRP (P = 0.019) and IL-1RA (P = 0.013).Conclusions: Adiponectin concentrations in women decreased relatively more compared with men across individuals with normal glucose tolerance, prediabetes, and type 2 diabetes, whereas inflammatory markers increased relatively more in women. Higher inflammatory stress in women than in men with prediabetes and type 2 diabetes may explain their relatively higher cardiovascular disease risk.     

The Relationship Between Adverse Childhood Experiences and Diabetes in Central Michigan Adults

Objective: Adverse childhood experiences (ACEs) predispose individuals to poor health outcomes as adults. Although a dose-response relationship between the number of ACEs and certain chronic illnesses has been shown, the impact of ACEs on diabetes is not thoroughly understood. We investigated the prevalence of ACEs in patients with diabetes and the potential relationship to the severity of diabetes.Methods: Patients with diabetes (both type 1 and type 2) or obesity were surveyed from the Endocrinology & Diabetes Center at McLaren Central Michigan in Mount Pleasant, Michigan. A validated, standard ACE questionnaire was administered to quantify the number of adverse childhood events that patients have experienced. A retrospective chart analysis was then conducted, addressing the relationship of ACEs with the severity of disease in the diabetes group and the obesity group. The number of ACEs was correlated with disease comorbidities, complications, and measurable quantities, such as body mass index (BMI) and hemoglobin A1c (HbA1c).Results: ACE scores in both diabetes and obesity groups were shown to have a greater prevalence compared to the general ACE average in Michigan. ACE scores also positively correlated to BMI and HbA1c in the diabetes group. Those with higher ACE scores in the diabetes group were also more likely to have depression and anxiety.Conclusion:ACE screening may lead to a greater understanding of the severity of and progression of diabetes. Ultimately, these results could provide support to potential interventional studies leading to the altered management of diabetes in patients with ACEs, or preventative intervention to children with ACEs.Abbreviations: ACE = adverse childhood experiences; BMI = body mass index; HbA1c = hemoglobin A1c; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Hba1C Control And Cost-Effectiveness in Patients With Type 2 Diabetes Mellitus Initiated On Canagliflozin or A Glucagon-Like Peptide 1 Receptor Agonist in A Real-World Setting

Objective: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting.Methods: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012–April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics. HbA1c levels at 3-month intervals were compared using generalized estimating equations. Medication costs used wholesale acquisition costs.Results: For both cohorts (CANA: n = 11,435; GLP-1 RA: n = 11,582), HbA1c levels decreased at 3 months postindex and remained lower through 30 months. Absolute changes in mean HbA1c from index to 3 months postindex for CANA and GLP-1 RA were -1.16% and -1.21% (patients with baseline HbA1c ≥7% &lsqb;53 mmol/mol]); -1.54% and -1.51% (patients with baseline HbA1c ≥8% &lsqb;64 mmol/mol]); and -2.13% and -1.99% (patients with baseline HbA1c ≥9% &lsqb;75 mmol/mol]), respectively. Postindex, CANA patients with baseline HbA1c ≥7% had similar HbA1c levels at each interval versus GLP-1 RA patients, except 9 months (mean HbA1c, 7.75% &lsqb;61 mmol/mol] vs. 7.86% &lsqb;62 mmol/mol]; P = .0305). CANA patients with baseline HbA1c ≥8% and ≥9% had consistently lower HbA1c numerically versus GLP-1 RA patients and statistically lower HbA1c at 9 (baseline HbA1c ≥8% or ≥9%), 27, and 30 months (baseline HbA1c ≥9%). Continuous 12-month medication cost $3,326 less for CANA versus GLP-1 RA.Conclusion: This retrospective study demonstrated a similar evolution of HbA1c levels among CANA and GLP-1 RA patients in a real-world setting. Lower medication costs suggest CANA is economically dominant over GLP-1 RA (similar effectiveness, lower cost).Abbreviations:AHA = antihyperglycemic agentBMI = body mass indexCANA = canagliflozin 300 mgDCSI = diabetes complications severity indexeGFR = estimated glomerular filtration rateEMR = electronic medical recordGLP-1 RA = glucagon-like peptide 1 receptor agonistHbA1c = glycated hemoglobinICD-9-CM = International Classification of Diseases–Ninth Revision–Clinical ModificationICD-10-CM = International Classification of Diseases–Tenth Revision–Clinical ModificationIPTW = inverse probability of treatment weightingITT = intent-to-treatMPR = medication possession ratioPDC = proportion of days coveredPS = propensity scorePSM = propensity score matchingQuan-CCI = Quan-Charlson comorbidity indexSGLT2 = sodium-glucose cotransporter 2T2DM = type 2 diabetes mellitusWAC = wholesale acquisition cost     

Identifying Probable Diabetes Mellitus Among Hispanics/Latinos from Four U.S. Cities: Findings from the Hispanic Community Health Study/Study of Latinos

Objective: The aim of this study was to compare the ability of American Diabetes Association (ADA) diagnostic criteria to identify U.S. Hispanics/Latinos from diverse heritage groups with probable diabetes mellitus and assess cardiovascular risk factor correlates of those criteria.Methods: Cross-sectional analysis of data from 15,507 adults from 6 Hispanic/Latino heritage groups, enrolled in the Hispanic Community Health Study/Study of Latinos. The prevalence of probable diabetes mellitus was estimated using individual or combinations of ADA-defined cut points. The sensitivity and specificity of these criteria at identifying diabetes mellitus from ADA-defined prediabetes and normoglycemia were evaluated. Prevalence ratios of hypertension, abnormal lipids, and elevated urinary albumin-creatinine ratio for unrecognized diabetes mellitus—versus prediabetes and normoglycemia—were calculated.Results: Among Hispanics/Latinos (mean age, 43 years) with diabetes mellitus, 39.4% met laboratory test criteria for probable diabetes, and the prevalence varied by heritage group. Using the oral glucose tolerance test as the gold standard, the sensitivity of fasting plasma glucose (FPG) and hemoglobin A1c—alone or in combination—was low (18, 23, and 33%, respectively) at identifying probable diabetes mellitus. Individuals who met any criterion for probable diabetes mellitus had significantly higher (P<.05) prevalence of most cardiovascular risk factors than those with normoglycemia or prediabetes, and this association was not modified by Hispanic/Latino heritage group.Conclusion: FPG and hemoglobin A1c are not sensitive (but are highly specific) at detecting probable diabetes mellitus among Hispanics/Latinos, independent of heritage group. Assessing cardiovascular risk factors at diagnosis might prompt multitarget interventions and reduce health complications in this young population.Abbreviations:2hPG = 2-hour post–glucose load plasma glucoseADA = American Diabetes AssociationBMI = body mass indexCV = cardiovascularFPG = fasting plasma glucoseHbA1c = hemoglobin A1cHCHS/SOL = Hispanic Community Health Study/Study of LatinosHDL-C = high-density-lipoprotein cholesterolNGT = normal glucose toleranceNHANES = National Health and Nutrition Examination SurveyOGTT = oral glucose tolerance testTG = triglycerideUACR = urine albumin-creatinine ratio     

Real-World Implications of Hybrid Close Loop (Hcl) Insulin Delivery System

Objective: Clinical trial data demonstrates improved glycemic control with hybrid close loop (HCL) insulin delivery systems, yet limited real-world data exists. Data from the inaugural cohort of patients initiating a HCL system (Medtronic MiniMed™ 670G, Medtronic Canada, Brampton, ON) at a university medical center was used to examine real-world utilization and glycemic control following a standardized implementation process.Methods: Data from 34 adult patients with type 1 diabetes were obtained from pump downloads at 4 time points: (1) previous insulin pump, (2) HCL in manual-mode, (3) 2 weeks after HCL auto-mode transition, and (4) 6 to 12 weeks after initiation of HCL. In-person training by certified diabetes educators was performed across 3 sessions with phone and electronic messaging following auto-mode start.Results: Mean self-monitored blood glucose (SMBG) per day increased from 5.15 baseline to 6.49 at 6 to 12 weeks (P<.05) with 3.26 sensor calibrations per day. Time-in-auto-mode was 79.3% at 2 weeks and 72.3% at final follow-up, with 82% of patients spending >50% of time in auto-mode. There were 8.2 auto-mode exits over the final 14-day download. Time-in-target was 67.3% in manual-mode, 73.4% at 2 weeks (P = .09), and 71.7% by 6 to 12 weeks (P = .06). Hemoglobin A1c (HbA1c) decreased by 0.51% (P = .02), while total daily dose and % basal did not change. Patients with HbA1c <7.0% (53 mmol/mol) at baseline spent more time-in-target than those with HbA1c ≥7.0% (53 mmol/mol; 78.0% versus 67.5%) despite spending less time-in-auto-mode (66.5% versus 74.8%).Conclusion: These data illustrate real-world implementation of HCL technology using a structured education program within a major medical center. Overall benefit may vary based on baseline characteristics such as HbA1c.Abbreviations: CDE = certified diabetes educator; HbA1c = hemoglobin A1c; HCL = hybrid closed loop; SMBG = self-monitored blood glucose     

EXOGENOUS TESTOSTERONE DOES NOT INDUCE OR EXACERBATE THE METABOLIC FEATURES ASSOCIATED WITH PCOS AMONG TRANSGENDER MEN

Objective: Polycystic ovary syndrome (PCOS) is a complex condition which can include menstrual irregularity, metabolic derangement, and increased androgen levels. The mechanism of PCOS is unknown. Some suggest that excess production of androgens by the ovaries may cause or exacerbate the metabolic findings. The purpose of this study was to assess the role of increased testosterone on metabolic parameters for individuals presumed to be chromosomally female by examination of these parameters in hormone-treated transgender men.Methods: In 2015 and 2016, we asked all transgender men who visited the Endocrinology Clinic at Boston Medical Center treated with testosterone for consent for a retrospective anonymous chart review. Of the 36 men, 34 agreed (94%). Serum metabolic factors and body mass index (BMI) levels for each patient were graphed over time, from initiation of therapy through 6 years of treatment. Bivariate analyses were conducted to analyze the impact of added testosterone.Results: Regressions measuring the impact of testosterone demonstrated no significant changes in levels of glycated hemoglobin (HbA1c), triglycerides, or low-density-lipoprotein cholesterol. There was a statistically significant decrease in BMI with increasing testosterone. There was also a statistically significant decrease in high-density lipoprotein levels upon initiation of testosterone therapy.Conclusion: Testosterone therapy in transgender men across a wide range of doses and over many years did not result in the dyslipidemia or abnormalities in HbA1c seen with PCOS. Instead, treatment of transgender men with testosterone resulted only in a shift of metabolic biomarkers toward the average physiologic male body.Abbreviations: BMI = body mass index; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; PCOS = polycystic ovary syndrome     

SGLT-2 Inhibitor Therapy Added to GLP-1 Agonist Therapy in the Management of T2DM

Objective: To assess the real-world efficacy and safety of canagliflozin therapy added to type 2 diabetes mellitus (T2DM) patients who have received a minimum 1 year of glucagon-like peptide-1 (GLP-1) agonist therapy.Methods: This pre-post observational study assessed the efficacy and safety of canagliflozin in a group of T2DM patients from a community endocrinology practice who received GLP-1 agonist therapy for a minimum of 12 months. The primary study outcome was change in mean glycated hemoglobin (HbA1c) level from baseline. Secondary endpoints included changes in average weight, and comparison of the percentage of patients obtaining an HbA1c <7%.Results: A total of 75 patients met all the study criteria. Baseline patient characteristics were as follows: average age, 58 ± 9 years; mean duration of T2DM, 14 ± 6 years; 56% male; 92% Caucasian; baseline body mass index (BMI), 39.4 ± 9.4 kg/m²; and mean baseline HbA1c, 7.94 ± 0.69%. HbA1c and weight were significantly reduced by 0.39% and 4.6 kg, respectively. Adverse effects were reported by 13 (17.3%) patients, including 4 (5.3%) who discontinued canagliflozin because of adverse reactions.Conclusion: Canagliflozin was generally well tolerated and significantly further reduced mean HbA1c levels and body weight in patients with T2DM when added to GLP-1 regimen.Abbreviations:BP = blood pressureBUN = blood urea nitrogenCANTATA = Canagliflozin Treatment and Trial AnalysisDBP = diastolic blood pressureDKA = diabetic ketoacidosisDPP-4 = dipeptidyl peptidase-4EMR = electronic medical recordFDA = Food and Drug AdministrationGFR = glomerular filtration rateGLP-1 = glucagon-like peptide-1HbA1c = glycated hemoglobinHDL-C = high-density lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterolSCr = serum creatinineSGLT-2 = sodium glucose cotransporter 2T2DM = type 2 diabetes mellitusTZD = thiazolidinedioneUTI = urinary tract infection     

The Impact of GLP-1 Receptor Agonists on Patients with Diabetes on Insulin Therapy

Objective: The clinical benefit of adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to basal-bolus or very high dose insulin regimens is unclear. This study investigated the impact of adding a GLP-1RA to a spectrum of insulin regimens (basal, basal-bolus, and U-500) to determine the impact on hemoglobin A1c (HbA1c), weight loss, and total daily insulin dose (TDD) over the course of 12 months.Methods: A retrospective chart review was conducted on 113 participants with type 2 diabetes mellitus using insulin therapy. Each participant's HbA1c, body weight, and TDD were recorded prior to initiation of GLP-1RA therapy and at the 3, 6, and 12-month time points while on combination therapy.Results: Across all participants, the HbA1c values decreased significantly from a baseline of 8.9 (74 mmol/mol) ± 0.14% to 8.2 (66 mmol/mol) ± 0.14% (P<.01) in the first 3 months, 8.0 (64 mmol/mol) ± 0.12% (P<.01) at 6 months, to 8.3 (67 mmol/mol) ± 0.14% (P<.01) at 12 months. There was no significant decrease in weight or TDD with the addition of a GLP-1RA overall or in different insulin groups. However, there was a clinically significant decrease in weight over the study duration.Conclusion: The results of this study suggest that adding a GLP-1RA to various insulin regimens may help to achieve glycemic goals while avoiding the less desirable side effects of weight gain and increasing insulin regimens. However, the expected weight loss and decrease in TDD may not be as sizable in the clinical setting.Abbreviations: DCOE = Diabetes Center of Excellence; DM = diabetes mellitus; GLP-1RA = glucagon-like peptide-1 receptor agonist; HbA1c = hemoglobin A1c; RCT = randomized controlled trial; TDD = total daily dose     

Open Access to Diabetes Center from the Emergency Department Reduces Hospitalizations in the Susequent Year

Objective: Patients who present to the emergency department (ED) for diabetes without hyperglycemic crisis are at risk of unnecessary hospitalizations and poor outcomes. To address this, the ED Diabetes Rapid-referral Program (EDRP) was designed to provide ED staff with direct booking into the diabetes center. The objective of this study was to determine the effects of the EDRP on hospitalization rate, ED utilization rate, glycemic control, and expenditures.Methods: We conducted a single-center analysis of the EDRP cohort (n = 420) and compared 1-year outcomes to historic controls (n = 791). We also compared EDRP patients who arrived (ARR) to those who did not show (NS). The primary outcome was hospitalization rate over 1 year. Secondary outcomes included ED recidivism rate, hemoglobin A1c (HbA1c), and healthcare expenditures.Results: Compared with controls, the EDRP cohort was less likely to be hospitalized (27.1% vs. 41.5%, P<.001) or return to the ED (52.2% vs. 62.3%, P = .001) at the end of 1 year. Total hospitalizations were also lower in the EDRP (157 ± 19 vs. 267 ± 18 per 1,000 persons per year, P<.001). The EDRP cohort had a greater reduction in HbA1c (-2.66 vs. -2.01%, P<.001), which was more pronounced when ARR patients were compared with NS (-2.71% vs. -1.37%, P<.05). The mean per patient institutional healthcare expenditures were lower by $5,461 compared with controls.Conclusion: Eliminating barriers to scheduling diabetes-focused ambulatory care for ED patients was associated with significant reductions in hospitalization rate, ED recidivism rate, HbA1c, and healthcare expenditures in the subsequent year.Abbreviations:ARR = arrivedED = emergency departmentEDRP = emergency department diabetes rapid-referral ProgramHbA1c = hemoglobin A1cNS = no show     

Regulation of Free Fatty Acid by Sitagliptin Monotherapy in DRUG-NAÏVE Subjects with Type 2 Diabetes

Objective: The aim of this study was to investigate the effects of sitagliptin on the regulation of free fatty acid (FFA) and other metabolic parameters in drug-naïve subjects with type 2 diabetes mellitus (T2DM).Methods: This was a prospective, nonrandomized, observational study. Drug-naïve subjects with T2DM received 25 to 50 mg/day sitagliptin monotherapy (n = 64). At 3 months, FFA and other metabolic parameters were compared with those at baseline. FFA was measured by colorimetry with enzymatic reactions. As a comparator, 12.5 to 25 mg/day alogliptin monotherapy was given to drug-naïve subjects with T2DM (n = 55).Results: Significant reductions in FFA (-13.2%, P<0.01) levels were observed with sitagliptin but not alogliptin. Both drugs showed similar glycemic efficacies. Significant correlations were observed between the changes (Δ) of FFA and Δglycated hemoglobin A1c (HbA1c), Dtotal cholesterol (TC), Δnon-high-density lipoprotein cholesterol (HDL-C), or Δlow-density lipoprotein cholesterol (LDL-C), and significant negative correlations were seen between ΔFFA and Δhomeostasis model assessment-B (HOMA-B), ΔC-peptide immunoreactivity (CPR)-index or Δbody mass index (BMI) in the sitagliptin group. The subjects in the sitagliptin group were further divided into 2 subgroups (n = 32 each) according to the changes of FFA (group B [above the median] ΔFFA = 23.1 %, P<.0005; group A [below the median] ΔFFA = -37.3 %, P<.00001). At baseline, FFA levels were significantly higher in group A versus group B (P<.001). Higher degrees of reductions of FBG (-14.6% vs. -9.3%, P<0.05) or HbA1c (-20.6% vs. -16.9%, P<.05), and increases of HOMA-B (52.7% vs. 38.3%, P<.03) or CPR-index (37.5% vs. 18.8%, P<.02) were observed in group A versus group B. Significant reductions of TC (-5.8%, P<.002), non-HDL-C (-7.8%, P<.001) or LDL-C (-6.3%, P<.02), and significant increases of C-peptide (11.3%, P<.05) were seen only in group A.Conclusion: Sitagliptin could downregulate high FFA levels. Subjects with reductions of FFA levels had better glycemic efficacies and higher degrees of enhancement of beta-cell function than others. Reductions of atherogenic cholesterols were seen in these populations.Abbreviations: CPR = C-peptide immunoreactivity; DPP-4 = dipeptidyl peptidase 4; FBG = fasting blood glucose; FFA = free fatty acid; HbA1c = glycated hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; HOMA-R = homeostasis model assessment-R; HOMA-B = homeostasis model assessment-B; non-HDL-C = non-HDL-cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; T2DM = type 2 diabetes; TG = triglyceride; UA = uric acid