Total Body Adiposity,Triglycerides, and Leg Fat are Independent Risk Factors for Diabetic Peripheral Neuropathy in Chinese Patients with type 2 Diabetes Mellitus

Objective: To evaluate the risk factors associated with diabetic peripheral neuropathy (DPN) in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: Between January 2014 and December 2017, 107 participants who had obesity with T2DM and 349 participants who had normal weight with T2DM, matched for age, sex, and duration of diabetes, were recruited. The clinical and biochemical parameters were measured in each patient. DPN was diagnosed based on neuropathy symptom score and neuropathy deficit score. Motor and sensory nerve conduction velocities were measured by electromyography. Body fat mass was estimated by dual-energy X-ray absorptiometry, while hepatic steatosis was evaluated by ultrasonography.Results: The group with obesity had a significant higher prevalence of DPN (66.62%) than that (46.99%) of the group with normal weight. Compared to the patients with normal weight, the sural sensory nerve in the right lower limbs of the patients with obesity was more susceptible to damage. Hypertriglyceridemia in the patients with obesity was a significant independent risk factor for DPN (odds ratio &lsqb;OR], 3.90 &lsqb;95% confidence interval (CI), 1.01 to 15.02]; P = .04), while the duration of diabetes (OR, 1.33 &lsqb;95% CI, 1.07 to 1.65]; P<.01) and leg subcutaneous fat mass (OR, 0.72 &lsqb;95% CI, 0.57 to 0.90]; P<.01) in the patients with normal weight were independent risk factors for DPN. The presence of obesity alone in patients with T2DM could predict high DPN risk (OR, 3.09 &lsqb;95% CI, 1.11 to 8.65]; P = .04).Conclusion: Reducing total body adiposity and triglyceride levels, as well as avoiding leg subcutaneous fat atrophy, could be new prevention strategies for DPN in Chinese patients with T2DM.Abbreviations: ALB = albumin; ALT = alanine transaminase; AST = aspartate transaminase; AUC = area under the curve; AUCc-p/AUCglu = AUC of C-peptide/AUC of glucose; BMI = body mass index; BP = blood pressure; CI = confidence interval; Cr = creatinine; DBP = diastolic blood pressure; DPN = diabetic peripheral neuropathy; FC-P = fasting C-peptide; FPG = fasting plasma glucose; FFA = free fatty acid; γ-GGT = γ-glutamyl transferase; HbA1c = glycated hemoglobin A1c; HDL-C = high-density-lipoprotein cholesterol; ISI = insulin sensitivity index; ISSI-2 = insulin secretion-sensitivity index-2; LDL-C = low-density-lipoprotein cholesterol; MNCS = motor nerve conduction velocity; OGTT = oral glucose tolerance test; PG = plasma glucose; SAT = subcutaneous adipose tissue; SBP = systolic blood pressure; SNCS = sensory nerve conduction velocity; T2DM = type 2 diabetes mellitus; TC = total cholesterol; TG = triglyceride; UA = uric acid; VAT = visceral adipose tissue; WC = waist circumference     

Efficacy and Safety of Ideglira in Older Patients with Type 2 Diabetes

Objective: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years.Methods: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1–receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V).Results: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, -1.0% &lsqb;-1.5; -0.6]_{95% confidence interval &lsqb;CI]}, -0.8% &lsqb;-1.0; -0.5]_{95% CI}, and -0.9% &lsqb;-1.3; -0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 &lsqb;0.2; 1.6]_{95% CI} &lsqb;P = .242]; 0.3 &lsqb;0.1; 0.5]_{95% CI} &lsqb;P<.001], and 11.8 &lsqb;3.3; 42.8]_{95% CI} &lsqb;P<.001] for DUAL II, V, and III, respectively).Conclusion: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall.Abbreviations: A1C = hemoglobin A1C; AE = adverse event; CI = confidence interval; Degludec = insulin degludec; EOT = end of trial; ETD = estimated treatment difference; FPG = fasting plasma glucose; GLP-1RA = glucagon-like peptide 1 receptor agonist; IDegLira = insulin degludec/liraglutide; IGlar U100 = insulin glargine 100 U/mL; SU = sulfonylurea; T2D = type 2 diabetes     

Increased Bone Turnover in Type 2 Diabetes Patients Randomized to Bariatric Surgery Versus Medical Therapy at 5 Years

Objective: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial.Methods: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index &lsqb;BMI], 36.5 ± 3.6 kg/m²) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% &lsqb;78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed.Results: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB (P<.001) and 61.1 ± 90% in SG (P<.001) compared to 29.8 ± 93% in IMT (P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB (P<.001) and 71 ± 69% in SG (P<.001) compared to 43.8 ± 121.1% in IMT (P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients (P<.001). Increase in CTX correlated with decreased BMI in SG patients (P = .039).Conclusion: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients.Abbreviations: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione     

Diabetes Duration and the Efficacy and Safety of Insulin Glargine Versus Comparator Treatment in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the effect of diabetes duration on efficacy and safety in patients with type 2 diabetes mellitus (T2DM) using insulin glargine versus comparator (oral antidiabetic drugs [OADs], dietary changes, or other insulins).MethodsData were pooled from randomized controlled clinical trials conducted in adults with T2DM with at least 24-week treatment with insulin glargine or a comparator, where predefined insulin titration algorithms were utilized to achieve fasting plasma glucose (FPG) concentrations of ≤ 100 mg/dL. Glycated hemoglobin A1C (A1C), FPG, and insulin dose and safety (hypoglycemia) outcomes were analyzed.ResultsNine studies were included in the analysis of 2,930 patients. Patients with shorter duration of diabetes were more likely to have greater reductions in A1C compared with those who had longer-duration disease (P < .0001). Disease duration did not affect change in FPG concentrations (P = .9017), but lower weight-adjusted insulin dose was correlated with longer-duration disease (P < .0001). Patients with longer-duration diabetes had increased risks of symptomatic hypoglycemia, confirmed hypoglycemia (self-monitored blood glucose < 50 mg/dL and < 70 mg/dL), and nocturnal hypoglycemia (all P < .001). No significant relationship was found between severe hypoglycemia and duration of diabetes. However, treatment with insulin glargine lowered A1C values more effectively than comparator treatments with fewer hypoglycemic episodes.ConclusionPatients with shorter-duration T2DM better achieved target A1C levels and had less hypoglycemia than those with longer disease duration. Insulin glargine was associated with reduced A1C and fewer hypoglycemic events than comparators, regardless of disease duration. (Endocr Pract. 2014;20:120-128)     

Case Finding for Hypothyroidism Should Include Type 2 Diabetes and Metabolic Syndrome Patients: A Latin American Thyroid Society (LATS) Position Statement

Objective: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients.Methods: A search was made in PubMed using the following terms: “hypothyroidism” AND “diabetes” OR “metabolic syndrome.” The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected.Results: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio &lsqb;OR], 3.45; 95% confidence interval &lsqb;CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60).Conclusion: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients.Abbreviations: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

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     

Relationship of Adipokines and Proinflammatory Cytokines Among Asian Indians With Obesity and Youth Onset Type 2 Diabetes

Objective: It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y).Methods: We recruited individuals with T2DM-Y (age at onset <25 years) and age-matched normal glucose tolerance (NGT) subjects. Participants were further classified using Asia-Pacific body mass index cut-points for obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha &lsqb;TNF-α] and monocyte chemotactic protein-1 &lsqb;MCP-1]) across groups.Results: Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 μg/mL, P<.01), and higher leptin (3.6 vs. 5.4, 5.7, 7.9 μg/mL, P<.001) and MCP 1 (186 vs. 272, 340, 473 pg/mL, P<.001) respectively. However, TNF-α levels were higher only among nonobese T2DM-Y (112 pg/mL) and obese T2DM-Y (141 pg/mL, P<.01 for each). After adjusting for age, sex, waist, hypertension, homeostatic model assessment of insulin resistance (HOMA-IR), serum cholesterol, triglycerides, and family history of diabetes, adiponectin was associated with 33% and 41% lower odds of being nonobese T2DM and obese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM.Conclusion: In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.Abbreviations: BMI = body mass index CI = confidence interval FPG = fasting plasma glucose HOMA-IR = homeostatic model assessment of insulin resistance IGT = impaired glucose tolerance MCP-1 = monocyte chemotactic protein-1 NGT = normal glucose tolerance OGTT = oral glucose tolerance test OR = odds ratio T2DM-Y = youth-onset type 2 diabetes TNF-α = tumor necrosis factor-α     

Dysregulation Of The Hypothalamic-Pituitary-Adrenal Axis Increases Central Body Fat Accumulation In Males Affected By Diabetes Mellitus And Late-Onset Hypogonadism

Objective: Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH).Methods: Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered.Results: The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 &lsqb;interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 &lsqb;interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 &lsqb;P<.001]; β = 1.156 &lsqb;P<.001]; β = -7.675 &lsqb;P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH.Conclusion: Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation.Abbreviations:ACTH = adrenocorticotropic hormoneAUC = area under the curveCRH = corticotropin-releasing hormoneCT = computed tomographyDEXA = dual-energy X-ray absorptiometryDM = diabetes mellitusFH = functional hypercortisolismFH-LOH = subjects affected by functional hypercortisolismFSH = follicle-stimulating hormoneHPA = hypothalamic-pituitary-adrenalLH = luteinizing hormoneLOH = late-onset hypogonadismN-LOH = subjects not affected by functional hypercortisolismOST = overnight low-dose dexamethasone suppression testSHBG = sex hormone–binding globulinUFC = urinary free cortisol     

Pituitary Imaging By Mri and its Correlation with Biochemical Parameters in the Evaluation of Men with Hypogonadotropic Hypogonadism

Objective: A significant ambiguity still remains about which patient deserves a magnetic resonance imaging (MRI) scan of the pituitary during evaluation of hypogonadotropic hypogonadism (HH) in men.Methods: Retrospective case series of 175 men with HH referred over 6 years.Results: A total of 49.7% of men had total testosterone (TT) levels lower than the Endocrine Society threshold of 5.2 nmol/L. One-hundred forty-two patients (81.2%) had normal appearance of pituitary MRI, whereas others had different spectrum of abnormalities (empty sella &lsqb;n = 16], macroadenoma &lsqb;n = 8], microadenoma &lsqb;n = 8], and pituitary cyst &lsqb;n = 1]). In men with TT in the lowest quartile, MRI pituitary findings were not significantly different from men in the remaining quartiles (P = .50). Patients with raised prolactin had higher number of abnormal MRI findings (38.9% vs. 13.7%; P = .0014) and adenomatous lesions (macro and micro) (27.8% vs. 4.3%; P = .01) in comparison to men with normal prolactin. The prolactin levels (median &lsqb;interquartile range]) were highest in men with macroadenomas in both groups (9,950 &lsqb;915]; P = .007 and 300 &lsqb;68.0] mU/L; P = .02, respectively), with concomitant lower levels of other pituitary hormones. Multivariate logistic regression showed an association of abnormal pituitary MRI with insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) (odds ratio &lsqb;OR], 1.78 &lsqb;95% confidence interval (CI), 1.15 to 2.77]; P = .009) and prolactin (OR, 1.00 &lsqb;95% CI, 1.00 to 1.03]; P = .01).Conclusion: MRI of the pituitary is not warranted in all patients with HH, as the yield of identifiable abnormalities is quite low. Anatomic lesions are likely to be present only when low levels of TT (<5.2 nmol/L) are found concomitantly with high levels of prolactin and/or low IGF-1 SDS.Abbreviations: CI = confidence interval; FT4 = free thyroxine; GH = growth hormone; HH = hypogonadotropic hypogonadism; IGF-1 = insulin-like growth factor; LH = luteinizing hormone; MRI = magnetic resonance imaging; OR = odds ratio; SDS = standard deviation score; TSH = thyroid-stimulating hormone; TT = total testosterone     

The Effects of Perioperative Dexamethasone on Glycemic Control and Postoperative Outcomes

Objective: Perioperative glucocorticoids are commonly given to reduce pain and nausea in patients undergoing surgery. However, the glycemic effects of steroids and the potential effects on morbidity and mortality have not been systematically evaluated. This study investigated the association between perioperative dexamethasone and postoperative blood glucose, hospital length of stay (LOS), readmission rates, and 90-day survival.Methods: Data from 4,800 consecutive orthopedic surgery patients who underwent surgery between 2000 and 2016 within a single health system were analyzed retrospectively.Results: Patients with and without diabetes mellitus (DM) who were given a single dose of dexamethasone had higher rates of hyperglycemia during the first 24 hours after surgery as compared to those who did not receive dexamethasone (hazard ratio &lsqb;HR] was 1.81, and 95% confidence interval &lsqb;CI] was &lsqb;1.46, 2.24] for the DM cohort; HR 2.34, 95% CI &lsqb;1.66, 3.29] for the nonDM cohort). LOS was nearly 1 day shorter in patients who received dexamethasone (geometric mean ratio &lsqb;GMR] 0.79, 95% CI &lsqb;0.75, 0.83] for patients with DM; GMR 0.75, 95% CI &lsqb;0.72, 0.79] for patients without DM), and there was no difference in 90-day readmission rates. In patients without DM, dexamethasone was associated with a higher 90-day overall survival (99.07% versus 96.90%; P = .004).Conclusion: In patients with and without DM who undergo orthopedic surgery, perioperative dexamethasone was associated with a transiently higher risk of hyperglycemia. However, dexamethasone treatment was associated with a shorter LOS in patients with and without DM, and a higher overall 90-day survival rate in patients without DM, compared to patients who did not receive dexamethasone.Abbreviations: BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; DM = diabetes mellitus; GMR = geometric mean ratio; HR = hazard ratio; IV = intravenous; LOS = length of stay; POD = postoperative day     

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 Switching Youth With Diabetes to Insulin Degludec in Clinical Practice

Objective: Many youth with diabetes struggle to meet glycemic targets. The new ultralong duration of action of insulin degludec (iDeg) holds potential to ameliorate missed doses of basal insulin and improve glycemic control in youth with diabetes.Methods: A retrospective chart review was undertaken of youth age 13 to <24 years in our practice with type 1 diabetes (T1D) or type 2 diabetes (T2D) who had been switched from glargine or detemir to iDeg to evaluate the impact of this transition on glycemic control.Results: Glycated hemoglobin A1c (HbA1c) in youth with T1D (n = 82) remained stable during 6 months of treatment with iDeg (10.1 ± 2.11% &lsqb;87 ± 23 mmol/mol] at start of iDeg compared to 10.1 ± 2.12% &lsqb;87 ± 23 mmol/mol] at 6 months of treatment), whereas in youth with T2D (n = 16), HbA1c significantly declined from 10.6 ± 2.3% (92 ± 25 mmol/mol) to 8.3 ± 2.2% (67 ± 24 mmol/mol) (P = .0024).Conclusion: In youth switched to iDeg, which in our practice is commonly due to ineffectiveness of the patient's current regimen, the outcome differences we saw may be due to preserved beta-cell function in youth with T2D. It remains to be seen whether there are benefits of transition to iDeg in youth with T1D beyond glycemic outcomes, such as reduction in ketosis and episodes of diabetic ketoacidosis.Abbreviations: DKA = diabetic ketoacidosis; DPV = Diabetes-Patienten-Verlaufsdokumentation (German/Austrian Prospective Diabetes Follow-Up Registry); HbA1c = glycated hemoglobin A1c; iDeg = insulin degludec; T1D = type 1 diabetes; T2D = type 2 diabetes     

Association of Thyroid Function with Posttraumatic Stress Disorder: a Systematic Review and Meta-Analysis

Objective: To conduct a systematic review and meta-analysis describing the association of thyroid function with posttraumatic stress disorder (PTSD) in adults.Methods: The authors conducted a comprehensive search from databases’ inception to July 20, 2018. The meta-analysis included studies that reported mean values and standard deviation (SD) of thyroid hormone levels (thyroid-stimulating hormone &lsqb;TSH], free thyroxine &lsqb;FT4], free triiodothyronine &lsqb;FT3], total T4 &lsqb;TT4], and total T3 &lsqb;TT3]) in patients with PTSD compared with controls. Five reviewers worked independently, in duplicate, to determine study inclusion, extract data, and assess risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each variable. Random-effects models for meta-analyses were applied.Results: The meta-analysis included 10 observational studies at low-to-moderate risk of bias. Studies included 674 adults (373 PTSD, 301 controls). The meta-analytic estimates showed higher levels of FT3 (+0.28 pg/mL; P = .001) and TT3 (+18.90 ng/dL; P = .005) in patients with PTSD compared to controls. There were no differences in TSH, FT4, or TT4 levels between groups. In the subgroup analysis, patients with combat-related PTSD still had higher FT3 (+0.36 pg/mL; P = .0004) and higher TT3 (+31.62 ng/dL; P<.00001) compared with controls. Conversely, patients with non–combat-related PTSD did not have differences in FT3 or TT3 levels compared with controls.Conclusion: There is scarce evidence regarding the association of thyroid disorders with PTSD. These findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD.     

The Associations Between Hypovitaminosis D,Higher Pth Levels With Bone Mineral Densities,And Risk Of The 10-Year Probability Of Major Osteoporotic Fractures In Chinese Patients With T2Dm

Objective: In the current study, we investigated the vitamin D status, and its relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD), and the 10-year probability of fractures in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: This was a cross-sectional study of 785 patients. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D (25(OH)D) and intact PTH were also quantified. The 10-year probability of fracture risk (major osteoporotic fracture &lsqb;MOF] and hip fracture &lsqb;HF]) was assessed using the fracture risk assessment tool (FRAX).Results: The prevalence of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 ± 15.2 nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk than the inadequate groups. Lower 25(OH)D was associated with higher PTH (r = -0.126, P<.001). PTH was negatively correlated with BMDs at 3 sites and positively correlated with MOF and HF, but this relationship disappeared in the adequate subgroup. Multivariate stepwise regression analysis revealed that PTH was the determinant of MOF (standard β = 0.073, P = .010) and HF (standard β = 0.094, P = .004).Conclusion: Our results identified a significantly high rate of vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk factor responsible for the higher 10-year probability of osteoporotic fractures in diabetic patients, especially in those with lower vitamin D levels.Abbreviations: AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine; MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus; PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA = uric acid     

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)     

1,5-Anhydroglucitol and Neonatal Complications in Pregnancy Complicated by Diabetes

Objective: To determine the association of 1,5-anhydroglucitol (1,5-AG) with neonatal birth weight (NBW) and neonatal hypoglycemia (+NH) in pregnancies complicated by diabetes.Methods: We assessed a retrospective cohort of 102 females, 17 with gestational diabetes (GDM), 48 with type 1 diabetes mellitus (T1DM), and 37 with type 2 diabetes mellitus (T2DM). 1,5-AG and glycated hemoglobin A1C (A1C) values throughout pregnancy were extracted. Linear regression was used to assess their association with NBWs z-scores adjusting for maternal age, ethnicity and body mass index (BMI). +NH was defined by a note in the infant record, glucose <1.7 mmol/L in the first 24 h, or <2.5 mmol/L in the first 48 h after birth. A t test or Welch's approximate t test was used to compare the mean 1,5-AG and A1C of mothers with +NH versus those without (-NH), adjusted for gestational age and analyzed by diabetes type and across trimesters.Results: Mean 1,5-AG significantly differed across groups: T1DM 3.77 ± 2.82 μg/mL, T2DM 5.73 ± 4.38 μg/mL, GDM 8.89 ± 4.39 μg/mL (P<.0001), suggesting less glucose exposure in GDM relative to T1DM or T2DM. A negative linear association was found between mean 1,5-AG and z-scores (R= -0.28, P = .005. In contrast, the association between mean A1C and z-scores was weaker (R = 0.15, P = .14). The mean 1,5-AG tended to be lower in the +NH cohort versus -NH (P = .08), and this was statistically significant (P = .01) among subjects with GDM.Conclusion: The association of 1,5-AG with complications related to glycemic exposure supports the notion of its utility as an adjunct glycemic biomarker in pregnancies complicated by diabetes and across trimesters.Abbreviations: 1,5-AG = 1,5-anhydroglucitol A1C = glycated hemoglobin A1C BMI = body mass index CGM = continuous glucose monitoring GDM = gestational diabetes mellitus LGA = large for gestational age MICC = maternal and infant care unit NBW = neonatal birth weight NH = neonatal hypoglycemia PPH = postprandial hyperglycemia SMBG = self-monitoring of blood glucose T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus     

De-Intensification of Diabetes Treatment in Elderly Patients with Type 2 Diabetes Mellitus

Objective: De-intensification of diabetes treatment is recommended in elderly patients with tight glycemic control at high risk of hypoglycemia. However, rates of de-intensification in endocrine practice are unknown. We conducted a retrospective study to evaluate the rate of de-intensification of antidiabetic treatment in elderly patients with type 2 diabetes mellitus (T2DM) and tight glycemic control.Methods: All patients with ≥2 clinic visits over a 1-year period at a major academic diabetes center were included. De-intensification of diabetes treatment was defined as a decrease or discontinuation of any antidiabetic drug without adding another drug, or a reduction in the total daily dose of insulin or a sulfonylurea drug with or without adding a drug without risk of hypoglycemia.Results: Out of 3,186 unique patients, 492 were ≥65 years old with T2DM and hemoglobin A1c (HbA1c) <7.5% (<58 mmol/mol). We found 308 patients treated with a sulfonylurea drug or insulin, 102 of whom had hypoglycemia as per physician note. Among these 102 patients, 38 (37%) were advised to de-intensify therapy. In a subgroup analysis of patients ≥75 years old with HbA1c <7% (<53 mmol/mol), we found that out of 23 patients treated with a sulfonylurea drug or insulin and reporting hypoglycemia, 11 (43%) were advised de-intensification of therapy. There were no significant predictors of de-intensification of treatment.Conclusion: Our study suggests that de-intensification of antidiabetic medications is uncommon in elderly patients with T2DM. Strategies may need to be developed to prevent the potential harm of overtreatment in this population.Abbreviations: ADA = American Diabetes Association; CGM = continuous glucose monitoring; HbA1c = hemoglobin A1c; T2DM = type 2 diabetes mellitus; UKPDS = United Kingdom Prospective Diabetes Study     

Timing of GH Peak in Both Glucagon and Clonidine Tests is of Major Clinical Importance

Objective: To detect a possible correlation between timing of the peak value of growth hormone (GH) during stimulatory tests (STs) and the effectiveness of treatment with recombinant human growth hormone (rhGH) in children with idiopathic GH deficiency (iGHD).Methods: We retrospectively studied 92 patients with iGHD (57 boys; mean age at diagnosis: 9.93 years). Diagnosis was confirmed by 2 different STs, glucagon stimulation test (GST), and clonidine stimulation test (CST). Auxologic parameters were recorded, while observed and predicted (according to KIGS Prediction Model) height velocity during the first year of treatment and the index of responsiveness (IoR) were calculated for the prepubertal children (n = 65).Results: Atypical GST was defined as that with peak GH value at time 0 minutes, 30 minutes, 60 minutes, or 180 minutes, whereas atypical CST was defined as that with peak timing at 0 minutes, 30 minutes, or 120 minutes. Atypical GST was detected in 18 patients (19.57%). IoR was lower in the prepubertal children with atypical GST (-1.81 ± 0.67 versus -1.34 ± 0.85; P = .051). In the CST, the 18 children who had atypical timing, had significantly lower IoR (-1.86 ± 0.66 versus -1.35 ± 0.84; P = .047). When the patients were categorized according to the number of atypical tests, significant differences in the IoR were detected (-2.09 ± 0.68 with 2 atypical STs &lsqb;n = 6], -1.64 ± 0.61 with 1 atypical ST &lsqb;n = 16], and -1.29 ± 0.87 with no atypical ST &lsqb;n = 43], P = .045).Conclusion: The presence of atypical peak GH timing during ST may be a factor that predicts lower growth hormone velocity during the first year of rhGH treatment in prepubertal children with iGHD.Abbreviations: CST = clonidine stimulation test; GH = growth hormone; GHD = growth hormone deficiency; GST = glucagon stimulation test; iGHD = idiopathic growth hormone deficiency; IoR = index of responsiveness; rhGH = recombinant human growth hormone; SDS = standard deviation scores; ST = stimulatory test     

Prognostic Impact of Diabetes Mellitus on Overall Survival in a Nationwide Population-Based Cohort of Patients With Pancreatic Cancer

Objective: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality.Methods: This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (>2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed.Results: Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P<.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P<.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P<.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratio &lsqb;HR], 1.26; 95% confidence interval &lsqb;CI], 1.20 to 1.33; P<.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment.Conclusion: After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer.Abbreviations: CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database     

Patients Achieving Good Glycemic Control (HBA1c <7%) Experience A Lower Rate of Hypoglycemia With Insulin Degludec Than with Insulin Glargine: A Meta-Analysis of Phase 3A Trials

Objective: Meta-analysis to compare hypoglycemia rates of basal insulin degludec (IDeg) with insulin glargine (IGlar) in patients with diabetes achieving good glycemic control (hemoglobin A_1c [HbA_1c] <7% at end of trial).Methods: In a preplanned meta-analysis, patient data from 7 randomized, treat-to-target, 26- or 52-week trials in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) who administered IDeg (n = 2,899) or IGlar (n = 1,431) once daily were analyzed. Using a negative binomial regression model, this meta-analysis compared hypoglycemia rates in patients achieving HbA_1c <7% at end of trial with IDeg (n = 1,347) and IGlar (n = 697).Results: In all trials, IDeg was noninferior to IGlar in HbA_1c reduction from baseline. At end of trial, 2,044 patients (T2DM, n = 1,661; T1DM, n = 383) achieved HbA_1c <7%. The overall confirmed hypoglycemia rate, defined as plasma glucose <56 mg/dL or severe hypoglycemia if requiring assistance, was significantly lower with IDeg versus IGlar (estimated rate ratio [ERR] IDeg:IGlar, 0.86; 95% confidence interval [CI], 0.76 to 0.98). The nocturnal confirmed hypoglycemia rate, defined as occurring between midnight and 6:00 am, was significantly lower with IDeg (ERR, 0.63; 95% CI, 0.52 to 0.77). In the maintenance period (16 weeks onward when average insulin dose and glycemic levels stabilized), the overall confirmed hypoglycemia rate was significantly lower (ERR, 0.79; 95% CI, 0.68 to 0.92) and the nocturnal confirmed hypoglycemia rate was significantly lower (ERR, 0.57; 95% CI, 0.45 to 0.72) with IDeg versus IGlar.Conclusion: Patients with T1DM and T2DM achieved HbA_1c <7% with significantly lower rates of overall and nocturnal confirmed hypoglycemia with IDeg versus IGlar. The lower hypoglycemia rate with IDeg was more pronounced in the maintenance period.Abbreviations: ERR = estimated rate ratio; HbA_1c = hemoglobin A_1c; IDeg = insulin degludec; IGlar = insulin glargine; NPH = Neutral Protamine Hagedorn; PG = plasma glucose; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus