An Individualized Inpatient Diabetes Education and Hospital Transition Program for Poorly Controlled Hospitalized Patients with Diabetes

ObjectiveTo evaluate predictors of outcomes associated with an inpatient diabetes education and discharge support program for hospitalized patients with poorly controlled diabetes (glycated hemoglobin [HbA1c]>9%).MethodsPatients participated in individualized diabetes education conducted by a certified diabetes educator (CDE) that included an exploration of barriers and goal setting during hospitalization with telephone follow-up and communication with primary providers at discharge. Predictors of HbA1c reduction, successful follow-up, and readmission were analyzed.ResultsThere were 82 subjects, and 48% were insulin naïve. Patients with type 2 diabetes (T2D, n = 58) had a significant decrease in HbAlc at follow-up (-2.8%, P < .0001), while those with type 1 diabetes (T1D, n = 19) did not (+ 0.02%, P = .96). However, after adjustment for other factors, only increasing age, higher baseline HbA1c, earlier education, and initiation of basal insulin were significant predictors of reduction in HbA1c. Higher area level income and empowerment and earlier education were significant predictors of outpatient follow-up within 30 days. While 28% were admitted for severe hyperglycemia, only 1 patient was readmitted with severe hyperglycemia. Successful phone contact was 77% and 57% with and without the support of non-CDE assistants respectively, but all outcomes were similar.ConclusionThe study suggests that an individualized inpatient diabetes education and transition program is associated with a significant reduction in HbA1c that is dependent on baseline HbA1c, older age, initiation of insulin, and earlier enrollment. Additional interventions are needed to ensure better continuity of care. (Endocr Pract. 2014;20:1265-1273)     

Switching to basal-bolus insulin therapy is effective and safe in long-term type 2 diabetes patients inadequately controlled with other insulin regimens

AimTo assess in standard clinical practice the feasibility, efficacy, and safety of switching patients with long-standing type 2 diabetes (T2DM) and poor or unstable blood glucose control to basal-bolus insulin therapy.Material and methodsThis was a prospective, single center study including 37 patients with T2DM (age 65 ± 8 years, 62.2% men, body mass index 28.8 ± 6.2 kg/m², diabetes duration 18 ± 8 years) with poor or unstable glycemic control, who were switched to a basal-bolus insulin regimen with glargine and rapid-acting insulin analogue at the discretion of their physicians. After a group-structured outpatient diabetes training program, patients were followed in a clinical practice setting for 6 months. Clinical and biochemical variables were collected before switching and at 3 and 6 months.ResultsAfter switching to basal-bolus therapy, glycosylated hemoglobin (HbA1c) decreased from 9 ± 1.2% to 8.1 ± 1.2% (p < 0.001) at 3 months and to 8.0 ± 1.2% at 6 months (p < 0.001) without changing total daily insulin dose. The proportion of patients with HbA1c ≥ 9% decreased from 51% to 13.8% at 3 months and to 18.9% at 6 months respectively. There was a single episode of severe hypoglycemia. No changes were seen in body weight and quality of life. The size of LDL (low density lipoprotein) particles significantly increased at 3 and 6 months, while all other lipid parameters remained unchanged.ConclusionsOur study confirmed that basal-bolus insulin therapy is feasible, effective, and safe in patients with long-standing T2DM, and does not impair their quality of life.     

Effect of Bromocriptine-Qr On Glycemic Control in Subjects with Uncontrolled Hyperglycemia On One or Two Oral Anti-Diabetes Agents

ObjectiveTo investigate the effect of Bromocriptine QR on glycemic control in patients with type 2 diabetes whose glycemia is poorly controlled on one or two oral anti-diabetes agents.MethodsFive hundred fifteen Type 2 Diabetes Mellitus (T2DM) subjects (ages 18 to 80 and average body mass index [BMI] of 32.7) with baseline HbA1c ≥ 7.5 and on one or two oral anti-diabetes (OAD) medications (metformin, sulfonylurea, and/or thiazolidinediones) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 24 week treatment period. Study investigators were allowed to adjust, if necessary, subject anti diabetes medications during the study to attempt to achieve glycemic control in case of glycemic deterioration. The impact of bromocriptine-QR treatment intervention on glycemic control was assessed in subjects on any one or two OADs (ALL treatment category) (N = 515), or on metformin with or without another OAD (Met/OAD treatment category) (N = 356), or on metformin plus a sulfonylurea (Met/SU treatment category) (N = 245) 1) by examining the between group difference in change from baseline a) concomitant OAD medication changes during the study, and b) HbA1c and 2) by determining the odds of reaching HbA1c of ≤ 7.0% on bromocriptine-QR versus placebo.ResultsSignificantly more patients (approximately 1.5 to 2-fold more; P < .05) intensified concomitant anti diabetes medication therapy during the study in the placebo versus the bromocriptine-QR arm. In subjects that did not change the intensity of the baseline diabetes therapy (72%), and that were on any one or two OADs (ALL), or on metformin with or without another OAD (Met/OAD), or on metformin plus sulfonylurea (Met/SU), the HbA1c change for bromocriptine-QR versus placebo was − 0.47 versus + 0.22 (between group delta of − 0.69, P < .0001), − 0.55 versus + 0.26 (between group delta of − 0.81, P < .0001) and − 0.63 versus + 0.20 (between group delta of − 0.83, P < .0001) respectively, after 24 weeks on therapy. The odds ratio of reaching HbA1c of ≤ 7.0% was 6.50, 12.03 and 11.45 (P < .0002) for these three groups, respectively.ConclusionIn T2DM subjects whose hyperglycemia is poorly controlled on one or two oral agents, bromocrip tine-QR therapy for 24 weeks can provide significant added improvement in glycemic control relative to adding placebo. (Endocr Pract. 2012;18:931-943)     

Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study

BackgroundChromium is an essential mineral that contributes to normal glucose function and lipid metabolism. This study evaluated the effect of chromium picolinate (CrPic) supplementation in patients with type 2 diabetes mellitus (T2DM).MethodsA four month controlled, single blind, randomized trial was performed with 71 patients with poorly controlled (hemoglobin A1c [HbA1c] > 7%) T2DM divided into 2 groups: Control (n = 39, using placebo), and supplemented (n = 32, using 600 μg/day CrPic). All patients received nutritional guidance according to the American Diabetes Association (ADA), and kept using prescribed medications. Fasting and postprandial glucose, HbA1c, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and serum ferritin were evaluated.ResultsCrPic supplementation significantly reduced the fasting glucose concentration (−31.0 mg/dL supplemented group; −14.0 mg/dL control group; p < 0.05, post- vs. pre-treatment, in each group) and postprandial glucose concentration (−37.0 mg/dL in the supplemented group; −11.5 mg/dL in the control group; p < 0.05). HbA1c values were also significantly reduced in both groups (p < 0.001, comparing post- vs. pre-treatment groups). Post-treatment HbA1c values in supplemented patients were significantly lower than those of control patients. HbA1c lowering in the supplemented group (−1.90), and in the control group (−1.00), was also significant, comparing pre- and post-treatment values, for each group (p < 0.001 and p < 0.05, respectively). CrPic increased serum chromium concentrations (p < 0.001), when comparing the supplemented group before and after supplementation. No significant difference in lipid profile was observed in the supplemented group; however, total cholesterol, HDL-c and LDL-c were significantly lowered, comparing pre- and post-treatment period, in the control group (p < 0.05).ConclusionsCrPic supplementation had a beneficial effect on glycemic control in patients with poorly controlled T2DM, without affecting the lipid profile. Additional studies are necessary to investigate the effect of long-term CrPic supplementation.     

Metabolic control and chronic complications during a 3-year follow-up period in a cohort of type 2 diabetic patients attended in primary care in the Community of Madrid (Spain)

BackgroundOur aim was to analyze both metabolic control and chronic complications of type 2 diabetes mellitus (T2D) patients regularly attended in primary care during a 3 years of follow-up in the Community of Madrid (Spain).MethodsFrom 2007 to 2010 we prospectively included 3268 patients with T2D attended by 153 primary care physicians from 51 family health centers. An prospective cohort study with annual evaluation over 3 years to the same population was performed. We measured the goals of control in diabetic patients and the incidence of chronic complications of diabetes during the study period.ResultsA significant decrease in serum glucose levels (143 ± 42 mg/dl vs 137 ± 43 mg/dl, p < 0.00), HbA1c (7.09 ± 1.2% vs 7.02 ± 1.2%, p < 0.00), total cholesterol (191.4 ± 38 mg/dl vs 181.5 ± 36 mg/dl, p < 0.00), LDL cholesterol (114.7 ± 31 mg/dl vs 105.5 ± 30 mg/dl, p < 0.00) and triglyceride levels (144.5 ± 93 mg/dl vs 138 ± 84 mg/dl, p < 0.00) during study period was documented. On the contrary, a significant elevation in HDL cholesterol levels was observed (49.2 ± 14 mg/dl vs 49.9 ± 16 mg/dl, p < 0.00). The incidence of diabetic complications throughout the study period was low, with a incidence of coronary heart disease of 6.2%, peripheral arterial disease 3%, ischemic stroke 2.8%, diabetic foot 11.2%, nephropathy 5.9%, retinopathy 4.5%, and neuropathy 3%.ConclusionMetabolic control in T2D patients attended in primary care in the Community of Madrid throughout 3 years is adequate and is accompanied by low percent of chronic diabetic complications during this period of follow-up.     

Evaluación del grado de consecución de objetivos de control metabólico en pacientes con diabetes mellitus tipo 2

ObjectiveTo evaluate the extent to which metabolic targets in type 2 diabetes (DM-2) are achieved in the Endocrinology and Clinical Nutrition Unit of the Hospital Puerta del Mar in Cadiz (Spain) from 2005 to 2008.MethodThe database included in the computer application HP-Doctor used for all patients attended in our unit (admissions, consultations and peripheral centers) was analyzed. All patients with a principal or secondary diagnosis of DM-2 were included. Clinical characteristics, chronic complications, drug treatment and the percentage of patients who achieved annual mean targets of glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDLc) were analyzed.ResultsFrom 2005 to 2008, the number of DM-2 patients with computerized records increased by 108.7%. In 2008, 1,177 patients were evaluated. A total of 10.8% were active smokers, 53% had hypertension, and 51.2% and 12.6% presented with retinopathy and cardiovascular disease, respectively. During the study period, the percentage of patients with a mean HbA1c <7% was similar (2005: 31.7% 2008: 30.4%), those with LDLc <100 mg/dl increased from 19.2% to 25.6% and only 9.2% of patients achieved both targets, HbA1c <7% and LDLc <100 mg/dl.ConclusionsIn 2008, only 30% of DM-2 patients achieved a mean HbA1c < 7% and only 25% had LDLc < 100 mg/dl. Metabolic control in DM-2 patients should be improved.     

Frequency of Continuous Glucose Monitoring use and Change in Hemoglobin A1C for Adults With Type 1 Diabetes in a Clinical Practice Setting

ObjectiveTo estimate the frequency of continuous glucose monitoring (CGM) use and change in hemoglobin A1c (HbA1c) compared to self-monitoring of blood glucose (SMBG) alone in adults with type 1 diabetes in a clinical practice setting.MethodsWe retrospectively identified 66 adult type 1 diabetes patients at the Barbara Davis Center for Diabetes (BDC) who first initiated CGM between 2006 and 2011 and 67 controls using SMBG. The frequency of CGM use was estimated from survey recall and defined as the mean number of days/month of CGM use during a maximum follow-up of 10 months. Change in HbA1c was calculated as the difference between the baseline value and the lowest follow-up value.ResultsThe mean change in HbA1c for CGM users was − 0.48% (95% confidence interval [CI]: − 0.67, − 0.28) and for SMBG users was − 0.37% (95% CI: − 0.56, − 0.18). The between-group mean difference in change in HbA1c, adjusted for patient characteristics, was − 0.11% (95% CI: − 0.38, 0.16), whereas the subgroup with a baseline HbA1c ≥ 7.0% and users of CGM ≥ 21 days/month was − 0.36% (95% CI, − 0.78, 0.05). Nearly half (n = 32, 48%) used CGM < 21 days/month. The reasons for low frequency of CGM use or discontinuation included sensor costs, frequency of alarms, inaccuracy, and discomfort.ConclusionsThese CGM data from clinical practice suggest a trend toward decreasing HbA1c for adults with type 1 diabetes, especially in patients with higher baseline HbA1c and higher frequency of CGM use. Future studies are needed to assess the use of CGM in larger populations of clinical practice adult type 1 diabetes patients. (Endocr Pract. 2014;20:1007-1015)     

Evaluación de la utilización de las prestaciones específicas de los sistemas de infusión subcutánea de insulina y su relación con el control metabólico en pacientes con diabetes tipo 1

Background and objectivePatients with type 1 diabetes (T1DM) treated with continuous subcutaneous insulin infusion (CSII) have available several specific features of these devices. The aim of this study was to evaluate the relationship between real use of them and the degree of glycemic control in patients using this therapy.Patients and methodsForty-four T1DM patients on CSII therapy with or without real-time continuous glucose monitoring (CGM) were included. Data from 14 consecutive days were retrospectively collected using the therapy management software CareLink Personal/Pro^® and HbA1c measurement performed at that period. The relationship between the frequency of usie of specific features of insulin pumps (non-sensor augmented or sensor-augmented) and glycemic control was analyzed.ResultsMean HbA1c in the group was 7.5 ± .8%. Mean daily number of boluses administered was 5.1 ± 1.8, with 75.4% of them being bolus wizards (BW). Daily number of boluses was significantly greater in patients with HbA1c < 7.5% than in those with HbA1c > 7.5% (5.3 ± 1.6 vs. 4.3 ± 1.6, P = .056). There was a trend to greater use of BW in patients with better control (82.8 ± 21.4% vs. 69.9 ± 29.1%, P = .106). HbA1c was lower in patients using CGM (n = 8) as compared to those not using sensor-augmented pumps (7.6 ± .8 vs 7.1 ± .7, P = .067), but the difference was not statistically significant.ConclusionsMore frequent use of BW appears to be associated to better metabolic control in patients with T1DM using pump therapy. In standard clinical practice, augmentation of insulin pump with CGM may be associated to improved glycemic control.     

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     

Pauta óptima de administración de insulina detemir en sujetos diabéticos tipo 1 con mal control metabólico

AimTo compare different administration times of insulin detemir (IDet) in patients with type 1 diabetes and poor metabolic control.Material and MethodsThis 24-week open study included 39 people with type 1 diabetes mellitus (DM) randomized to one injection of IDet before lunch (mean 14.24 ± 00.36 (± SD) h) or at bedtime (23.19 ± 0.42 h). Whenever target glycemia levels were not reached, the regimen was switched to insulin therapy with two injections (IDet-12 h). Insulin aspart was used before main meals.ResultsAt week 24, only 12.2% of patients remained in the IDet bedtime group and 30.3% in the IDet before lunch group. The remaining 57.5% joined the IDet-12 h group. There were no differences between the IDet before lunch and IDet bedtime groups. A subanalysis including the three groups demonstrated better metabolic control in the IDet before lunch group (glycosylated hemoglobin (HbA1c) 7.1 ± 0.2 vs. 7.6 ± 0.4 and 8.1 ± 0.2% in IDet before-lunch, IDet bedtime and IDet-12 h, respectively; p<0.05). An HbA1c value below 7% was achieved in 30.3% of the patients: 15.2% in the IDet before-lunch group, 3.3% in the IDet bedtime group and 12.2% in IDet-12 h group. Quality of life did not differ among treatment groups.ConclusionsOne injection of IDet administered before lunch could improve metabolic control. However, most patients required two injections of IDet.     

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds

ObjectivesWomen with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity.MethodsPCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA_1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]).ResultsIn 2006, ≤ 25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile < 20%; ALT/AST ≤ 25%. By 2011, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P < .0001; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P < .0001). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P < .05).ConclusionDespite the publication of recommendations in 2005, screening rates for metabolic disease in women with PCOS remained low across all race-ethnicities in 2011. (Endocr Pract. 2014;20:855-863)     

Caracterización y costes asociados al perfil del paciente con diabetes tipo 2 en tratamiento con metformina al que se le añade un segundo fármaco antidiabético oral: estudio de base poblacional

ObjectivesTo determine compliance, metabolic control, complications and healthcare costs of patients treated with metformin started a second antidiabetic drug in patients with type 2 diabetes (T2DM).Patients and methodsDesign multicenter observational retrospective. Patients were evaluated ≥30 years (age), treated with metformin and started a second antidiabetic treatment during 2008-2009. There were 4 patient groups (metformin and another antidiabetic): a) dipeptidyl peptidase-4 inhibitors (IDPP4), b) sulfonylureas, c) glitazones and d) insulin. Main measures: comorbidity, metabolic control, compliance and complications. Patients were followed for 2 years. The cost model differed direct health costs (primary care / specialist) and indirect (labor productivity). Statistical analysis: logistic regression models and ANCOVA, p < 0.05.Results2067 patients were included (mean age: 66.6 years male: 53.1%). 25.1% started a second treatment with IDPP4; 42.9% sulfonylureas, 14.0% glitazones and 18.0% insulin. At 2 years follow-up, patients treated with IDPP4 showed greater adherence vs. 70.3%. 59.9%, 60.3% and 58.4; better control of 64.3% vs. DM2. 62.6%, 62.8% and 50.5% and a decrease of 13.9% compared to hypoglycaemia 40.4%, 37.6% and 58.9% respectively (p < 0.001). The average / unit total costs was €2,321 vs. €2,475, €2,724 and €3,164, respectively, p < 0.001. Rates of cardiovascular events and renal failure were 3.7%, 6.4%, 7.6% and 10.2% respectively.ConclusionsSulfonylureas were the most commonly used drugs. Patients treated with IDPP4 had higher compliance and control of diabetes, with lower rates of hypoglycaemia and healthcare costs.     

Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

ObjectivesZinc may play a role in the development of type 2 diabetes (T2D), because it is involved in antioxidant and anti-inflammatory activities. However, the role of zinc in the etiology of T2D has been poorly investigated. This study was conducted to study the association of serum zinc on T2D risk in middle-aged and older Finnish men.MethodsThis was a 20-year prospective follow-up study on 2220 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) who were 42 to 60 years old at baseline in 1984–1989. The main outcome was incident T2D. Serum zinc, body mass index (BMI), fasting blood glucose (FBG), serum insulin, C-reactive protein (CRP) and, in a subset of 751 participants, insulin-like growth factor-binding protein-1 (IGFBP-1), were measured. Also, the homeostatic model assessment (HOMA) was used to quantify insulin resistance (HOMA-IR), beta-cell function (HOMA-β) and insulin sensitivity (HOMA-IS).ResultsAt baseline, serum zinc was associated with higher BMI, serum insulin, HOMA-IR, HOMA-β and IGFBP-1 and lower HOMA-IS. During the average follow-up of 19.3 years, 416 men developed T2D. Men in the highest quartile of serum zinc had 60% higher risk (95% CI 20–113%; P-trend < 0.001) for incident T2D compared with the men in the lowest quartile, after multivariate adjustments. This association was attenuated after adjustment for BMI (HR = 1.39, 95% CI 1.04–1.85; P-trend = 0.013) or HOMA-IS (HR = 1.38, 95% CI 1.04–1.83; P-trend = 0.015), whereas adjustment for the other factors had only modest impact on the association.ConclusionHigher serum zinc was associated with higher risk of T2D; effects of zinc on BMI and insulin sensitivity may partly explain the association. Further prospective studies are warranted to confirm our results and explore potential mechanisms.     

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)     

Clinical Profile of Nonalcoholic Fatty Liver Disease Among Young Patients With Type 1 Diabetes Mellitus Seen at a Diabetes Speciality Center in India

ObjectiveTo estimate the prevalence and clinical profile of nonalcoholic fatty liver disease (NAFLD) among young type 1 diabetes mellitus (T1DM) patients at a tertiary care diabetes center in India.MethodsElectronic medical records of T1DM patients (age at first diagnosis of T1DM ≤ 25 years) registered between January 1992 and May 2013 who had undergone ultrasonography and denied history of any alcohol intake (n = 736) were reviewed. NAFLD was diagnosed if there was any degree of fatty liver. Retinopathy was initially assessed by direct and indirect ophthalmoscopy and later by retinal photography. Nephropathy was diagnosed if urine protein excretion was > 500 mg/day, and neuropathy was diagnosed if a patient’s vibration perception threshold on biothesiometry was ≥ 20 V.ResultsA total of 204/736 (27.7%) T1DM patients had NAFLD. Compared to T1DM subjects without NAFLD those with NAFLD had higher body mass index (BMI) (18.9 ± 4.2 vs. 20.2 ± 4.7 kg/m², P < .001), waist circumference (67.9 ± 13.2 vs. 71.9 ± 13.3 cm, P < .05), systolic blood pressure (110 ± 15 vs. 116 ± 18 mm Hg, P < .001) and diastolic blood pressure (72 ± 9 vs. 74 ± 10 mm Hg, P < .05), while fasting blood glucose (201 ± 101 vs. 183 ± 101 mg/dL, P < .05) and alkaline phosphatase (419 [12.5] vs. 315 [15.8], P < .001) levels were lower in patients with T1DM with NAFLD. Multiple logistic regression analysis showed a significant association between NAFLD and retinopathy (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.13-3.43; P = .017, after adjusting for sex, duration of diabetes, overweight/obesity, hypertension, fasting plasma glucose, nephropathy, and nephropathy (OR: 1.89, 95% CI: 1.02-3.50; P = .042), after adjusting for sex and fasting plasma glucose.ConclusionsThis study suggests that NAFLD is also seen among T1DM patients and that it has an independent and significant association with retinopathy and nephropathy. (Endocr Pract. 2014;20:1249-1257)     

Safety and Efficacy of Exenatide in Combination with Insulin in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the 1-year efficacy and safety of treatment with exenatide in combination with insulin (a use not approved by the US Food and Drug Administration).MethodsElectronic medical records of 3 private-practice endocrinologists were reviewed to identify patients with type 2 diabetes mellitus (T2DM) receiving insulin who subsequently began exenatide therapy. Patients’ baseline hemoglobin A1c (A1C) levels, weights, lipid profiles, blood pressures, and medication utilization were compared with corresponding data obtained after a minimal duration of 12 months.ResultsWe identified 134 patients with T2DM initiating exenatide therapy in combination with insulin between April 2005 and April 2006. One-year follow-up information was available for 124 patients. Exenatide use resulted in a significant 0.87% reduction in A1C (P < .001), despite a 45% discontinuation of premeal insulin use (P < .001), a 9-U reduction in mean premeal insulin doses (P = .0066), a reduction in the median number of daily insulin injections from 2 to 1 (P = .0053), and a 59% discontinuation rate of sulfonylurea use (P = .0088). Exenatide use was associated with a mean weight loss of 5.2 kg (P < .001), with 72% of evaluable patients losing weight. Forty-eight patients (36%) discontinued exenatide therapy during the first year, primarily attributable to gastrointestinal intolerance. Fourteen patients (10%) experienced hypoglycemia, most of which was mild.ConclusionExenatide in combination with insulin in patients with T2DM was associated with significant reductions in A1C and weight after 1 year of therapy. This was offset, however, by an exenatide discontinuation rate of 36%, primarily due to adverse gastrointestinal effects. (Endocr Pract. 2008;14:285-292)     

Colesevelam Hydrochloride Added to Background Metformin Therapy in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from 3 Clinical Studies

ObjectiveTo evaluate the glucose- and lipid-altering efficacy of colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM).MethodsThis post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo- controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin.ResultsIn this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to receive placebo. In comparison with placebo, colesevelam HCl significantly reduced hemoglobin A_1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P < .001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P < .0001 for all). Median triglyceride levels were increased with colesevelam HCl (median treatment difference: + 12.8%; P < .0001). In comparison with placebo, colesevelam HCl significantly increased apo A-I (mean treatment difference: + 3.3%; P < .0001), whereas the mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated.ConclusionWhen added to metformin-including therapy, colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non- HDL-C, and apo B in patients with inadequately controlled T2DM. (Endocr Pract. 2011;17:933-938)     

Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes

Introduction/objectivesThe role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic.The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.MethodsPRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n = 8) at delivery and compared to controls (n = 5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n = 5) or nicotinamide (NCT) plus STZ (n = 9) or vehicle (n = 9). Placental whole-genome gene expression and PRL western blots were performed at birth.ResultsIn human placentas, PRL (p < 0.05) and BMP-1 (p < 0.01) gene expressions were increased with a higher amount of cleaved PRL (p < 0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT–STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p < 0.01) and Bmp-1 (p < 0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p < 0.05) and NCT–STZ (p < 0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women.ConclusionsAlterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.