Factores de riesgo cardiovascular en pacientes con hiperparatiroidismo primario asintomático

ObjectivesPatients with primary hyperparathyroidism (PHP), even asymptomatic, have an increased cardiovascular risk. However, data on reversibility or improvement of cardiovascular disorders with surgery are controversial. Our aims were to assess the prevalence of classic cardiovascular risk factors in patients with asymptomatic PHP, to explore their relationship with calcium and PTH levels, and analyze the effect of parathyroidectomy on those cardiovascular risk factors.Patients and methodsA retrospective, observational study of two groups of patients with asymptomatic PHP: 40 patients on observation and 33 patients who underwent surgery. Clinical and biochemical data related to PHP and various cardiovascular risk factors were collected from all patients at baseline and one year after surgery in the operated patients.ResultsA high prevalence of obesity (59.9%), type 2 diabetes mellitus (25%), high blood pressure (47.2%), and dyslipidemia (44.4%) was found in the total sample, with no difference between the study groups. Serum calcium and PTH levels positively correlated with BMI (r = .568, P = .011, and r = .509, P = .026 respectively) in non-operated patients. One year after parathyroidectomy, no improvement occurred in the cardiovascular risk factors considered.ConclusionsOur results confirm the high prevalence of obesity, type 2 diabetes mellitus, high blood pressure, and dyslipidemia in patients with asymptomatic PHP. However, parathyroidectomy did not improve these cardiovascular risk factors     

Alteraciones del metabolismo glucídico en el estudio de control de factores de riesgo de Extremadura (estudio COFRE)

AimsTo assess the prevalence and control of glucose metabolism disorders in a population of Extremadura (Spain) with at least one cardiovascular risk factor and to compare the characteristics of these patients with those who were normoglycemic in the risk factor control in Extremadura (COFRE study).Patients and methodsThe prevalence and control of cardiovascular risk factors were recorded in a sample of 1,022 patients with at least one cardiovascular risk factor consecutively visiting a primary care office. Of these, 951 patients were included in the analysis. In all patients, fasting glycemia was recorded. Glycated hemoglobin was recorded in diabetic patients.ResultsA total of 320 patients (33.6%) were previously known to be diabetic (DM) and 84 (8.8%) had glycemia ≥126 mg/dl without a previous diagnosis of diabetes (12 with glycemia above 200 mg/dl). Impaired fasting glycemia (IFG) was found in 211 (22.2%) and normoglycemia (NG) in 336 (35.3%). Within the DM group, glycemia <126 mg/dl was found in only 31.4% but glycated hemoglobin lower than 7% was found in 46.8%. Triglyceride concentrations were higher in the IFG group than in the NG group (137±65 mg/dL vs 124±65 mg/dL, p=0,041). Pulse pressure was also higher, but no differences were found in diastolic blood pressure (DBP) or heart rate. Differences in systolic blood pressure (SBP) were at the limit of significance (DM 139.5±17 vs NG 136.5±16 mmHg; p=0.056). No significant differences were found in any of these parameters between the DM and IFG groups.ConclusionsThe prevalence of glucose metabolism disorders was very high in the recruited sample. Patients with IFG showed higher pulse pressure and triglyceride concentrations than those with NG but there were no differences in comparison with DM patients. Diabetic control was poor when assessed by fasting glycemia but glycated hemoglobin showed better control.     

Prevalence of Sleep Apnea in a Population of Adults with Type 2 Diabetes Mellitus

ObjectiveTo assess the prevalence of sleep apnea (SA) in adults with type 2 diabetes mellitus (T2DM) and examine whether demographics and comorbid factors were associated with SA in this population.MethodsThis study enrolled 330 consecutive adults with T2DM referred to a diabetes clinic, 279 of whom completed the study. Evaluation of the presence of SA was performed with use of a single-channel recording device that measures disordered breathing events from a nasal cannula airflow signal. The device was worn by the study participants in their home, after instruction in appropriate use by clinical staff at the diabetes center. The presence and severity of SA were determined by use of an apnea-hypopnea index (AHI), reflecting periods of diminished and absent breathing. Demographic and medical information data were collected to detect factors associated with SA in this study population. In addition, a time and cost analysis was conducted regarding the screening process for SA by clinical staff at the diabetes center.ResultsThe results show a high prevalence of SA in adults with T2DM, ranging from 48% (AHI level of ≥ 10 events/h) to 29% (AHI level of ≥ 20 events/h). At an AHI cutoff value of ≥ 15 events/h, the overall prevalence rate was 36% (49% in male and 21% in female participants). The following variables were associated with SA: age ≥ 62 years, male sex, body mass index ≥ 30 kg/m², snoring, and reports of stopping breathing during sleep. The time and cost analysis showed that the screening device involved minimal setup time, was simple to use, and was a cost-effective method to screen for SA.ConclusionSA is a common disorder associated with major morbid conditions, including hypertension, obesity, cardiovascular disease, and insulin resistance. Predisposing factors for SA and T2DM are similar. This study showed that SA has a high prevalence in adults with T2DM and identified factors that may be associated with its presence in this population. Assessment for SA can be easily performed in an outpatient setting with a portable recording device such as the one used in this study. Screening for SA should be considered in the T2DM population. (Endocr Pract. 2007;13:355-362)     

Associations between diet quality, health status and diabetic complications in patients with type 2 diabetes and comorbid obesity

ObjectivePatients with type 2 diabetes (T2DM) demonstrate low dietary adherence and this is further aggravated with comorbid obesity. The aim of the present study was to assess diet quality in patients with T2DM and comorbid obesity compared to patients with T2DM alone and to examine the associations between comorbidities and diet quality.MethodsThe sample consisted of 59 adult patients with diabesity (T2DM and comorbid obesity) and 94 patients with T2DM alone. All diabetes comorbidities and complications were recorded and diet quality was assessed with the Healthy Eating Index (HEI).ResultsMean raw HEI of the diabese subjects was 81.9 ± 7.1 and the diabetic subjects was 80.2 ± 6.9. When HEI was adjusted to the sex, age and weight status, the diabese demonstrated a higher HEI. Among comorbidities, only renal disease decreased HEI. According to the principal component analysis of the total sample, adequate diet quality was explained by cardiovascular disease, cigarette smoking, alcohol consumption, peptic ulcer, sex, diabesity and diabetic foot syndrome. In the diabese, adequate HEI was explained by diabetic foot syndrome, smoking, drinking alcohol and having a family history of diabetes.ConclusionsAdult patients with T2DM demonstrate adequate diet quality. Different factors are associated with the adoption of a high quality diet between the diabese and the T2DM alone.     

Safe and Simple Emergency Department Discharge Therapy for Patients with Type 2 Diabetes Mellitus and Severe Hyperglycemia

ObjectiveTo investigate the safety and effectiveness of 2 simple discharge regimens for use in patients with type 2 diabetes mellitus (DM2) and severe hyperglycemia, who present to the emergency department (ED) and do not need to be admitted.MethodsWe conducted an 8-week, open-label, randomized controlled trial in 77 adult patients with DM2 and blood glucose levels of 300 to 700 mg/dL seen in a public hospital ED. Patients were randomly assigned to receive glipizide XL, 10 mg orally daily (G group), versus glipizide XL, 10 mg orally daily, plus insulin glargine, 10 U daily (G + G group). The primary outcome was to maintain safe fasting glucose and random glucose levels of < 350 and < 500 mg/dL up to 4 weeks and < 300 and < 400 mg/ dL, respectively, thereafter and to have no return ED visits (responders).ResultsBaseline characteristics were similar between the 2 treatment groups. The primary outcome was achieved in 87% of patients in both treatment groups. The enrollment mean blood glucose values of 440 and 467 mg/dL in the G and G + G groups, respectively, declined by the end of week 1 to 298 and 289 mg/dL and by week 8 to 140 and 135 mg/dL, respectively. Homeostasis model assessment of b-cell function and early insulin response improved 7-fold and 4-fold, respectively, in responders at the end of the 8-week study.ConclusionSulfonylurea with and without use of a small dose of insulin glargine rapidly improved blood glucose levels and b-cell function in patients with DM2. Use of sulfonylurea alone once daily can be considered a safe discharge regimen for such patients and an effective bridge between ED intervention and subsequent follow-up. (Endocr Pract. 2009;15:696-704)     

Effect of Metformin Therapy on Vitamin D and Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus

ObjectiveTo determine the effect of metformin on 25-hydroxyvitamin D [25(OH)D] and vitamin B₁₂ levels in patients with type 2 diabetes mellitus.MethodsWe performed a retrospective review of medical records of patients treated between 2003 and 2009 at Loyola University Medical Center, Maywood, Illinois, in both ambulatory primary care and endocrinology clinics. The study cohort consisted of 706 patients with type 2 diabetes mellitus who were 20 to 93 years old (mean age, 63 ± 13) and had a mean body mass index of 33.1 kg/m². Of these patients, 42% were treated with metformin, and 34% had been diagnosed with osteoporosis or osteopenia.ResultsPatients taking metformin had statistically significant lower vitamin B₁₂ levels than those not receiving metformin (P < .0001; 95% confidence interval [CI] = − 220 to − 84 pg/mL). No statistically significant difference was found between users and nonusers of metformin in regard to 25(OH)D levels when adjusted for variables (P = .297; 95% CI for mean difference = − 0.7 to 2.2 ng/mL). Metformin use did not adversely affect successful treatment of vitamin D deficiency in this patient population as a whole, nor did it affect the subgroup with osteoporosis (P = .956). The patients with osteoporosis had statistically significant lower baseline 25(OH)D levels in comparison with those without osteoporosis, when adjustments were made for all variables (P = .003; 95% CI = 0.7 to 3.5 ng/ mL).ConclusionThis study confirms the higher prevalence of vitamin B₁₂ deficiency in metformin-treated patients with type 2 diabetes than in those not treated with metformin. This study also suggests that vitamin D deficiency is not a clinical concern among metformin-treated patients with type 2 diabetes and that metformin does not negatively affect treatment of vitamin D deficiency in these patients. (Endocr Pract. 2012;18:179–184)     

High Incidence of Impaired Glucose Regulation in Patients With no Known History of Diabetes Mellitus But With Hyperglycemia After Undergoing a Cardiac Surgical Procedure

ObjectiveTo determine the implications of the presence of hyperglycemia after a cardiac surgical procedure in patients with no history of diabetes mellitus (DM).MethodsWe conducted a prospective study of 50 consecutive patients with no known history of DM who underwent a cardiac surgical procedure and had postoperative hyperglycemia (plasma glucose levels ≥ 110 mg/dL), requiring an insulin drip to achieve tight glucose control. These patients underwent a 2-hour oral glucose tolerance test (OGTT) at 6 weeks postoperatively to determine the percentage of subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or type 2 DM.ResultsOf the 50 patients, 32 (64%) were found to have persistent glucose dysregulation. On the basis of OGTT results, 20% had IFG, 16% had both IFG and IGT, 10% had only IGT, and 18% had type 2 DM. Of the patients with newly diagnosed diabetes, 89% had a 6-week postoperative fasting plasma glucose (FPG) concentration of < 126 mg/dL. There was a significant correlation between the preoperative FPG levels and the 6-week postoperative 2-hour OGTT glucose levels (P < .01). No correlation was found between the 6-week postoperative FPG levels and the 2-hour OGTT glucose levels (P = .26).ConclusionHyperglycemia after a cardiac surgical procedure implies a high risk of persistent glucose dysregulation. Preoperative FPG levels correlated better with 2-hour OGTT results than did the 6-week postoperative FPG values, but both were insensitive markers for diagnosing type 2 DM in these patients. In our cohort, hemoglobin A1c was not predictive of abnormalities of glucose metabolism. Our data support the need for performing a postoperative OGTT in patients with no known history of DM but the presence of hyperglycemia after a cardiac operation. (Endocr Pract. 2009;15:425-430)     

Tasa estimada de disposición de glucosa en pacientes menores de 18 años con diabetes mellitus tipo 1 y sobrepeso-obesidad

ObjectiveTo assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight.MethodsA total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age.ResultsNo significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3 ± 1.3 vs 10.1 ± 0.8 mg kg^-1min^-1; p < 0.01). Insulin dose was higher in overweight and obese children, especially in IU/m²/day (37.7 vs 36.1 vs 29.4 respectively; p < 0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5 mg/dL respectively; p < 0.01). No correlation was found between waist circumference and the different markers of insulin resistance.ConclusionsValues of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m²/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk.     

Identifying Risk Factors for Severe Hypoglycemia in Hospitalized Patients with Diabetes

ObjectiveSome of the deleterious effects of hypoglycemia in hospitalized patients include increased rates of mortality and longer length of stay. Our primary objective was to identify the risk factors associated with severe hypoglycemia to identify those patients at highest risk.MethodsThe medical records of 5,026 patients with diabetes mellitus (DM) admitted in 2010 were reviewed to identify those patients that developed severe hypoglycemia (blood glucose [BG] < 40 mg/dL). We performed c2 tests to assess statistical significance. Adjusted logical regression was used to determine the risk factors for hypoglycemia in the hospital.ResultsOut of 5,026 DM patients included in our review, 81 experienced severe hypoglycemia (1.6%). Statistically higher proportions of chronic kidney disease (CKD; 69.1% vs. 46.9%, P < .001), congestive heart failure (CHF; 48.1% vs. 28.5%, P < .001), sepsis (49.4% vs. 12.5%, P < .001), insulin use (45.7% vs. 26.04%, P = .000), type 1 DM (21% vs. 5.1%, P = .000), and cirrhosis (14.8% vs. 7.2%, P = .009) were seen in the severe hypoglycemic group compared to the nonsevere hypoglycemic group. Overall, 84% of patients who experienced an episode of severe hypoglycemia in the hospital (BG < 40 mg/dL) had a previous episode of hypoglycemia (BG < 70 mg/dL). The odds ratios (ORs) for type 1 DM, sepsis, previous hypoglycemia, and insulin use were 3.43 (95% confidence interval [CI] 1.81, 6.49), 2.64 (95% CI 1.6, 4.35), 46.1 (95% CI 24.76, 85.74), and 1.66 (95% CI 1.02, 2.69), respectively.ConclusionPrior episodes of hypoglycemia in the hospital, the presence of type 1 DM, insulin use, and sepsis were identified as independent risk factors for the development of severe hypoglycemia in the hospital. (Endocr Pract. 2014;20:1051-1056)     

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)     

Tomographie sténopéïque au 99mTc-MIBI dans l’hyperparathyroïdie primaire

PurposeThis prospective study was conducted to determine the interest of ^99mTc-MIBI pinhole SPECT compared with conventional SPECT, planar scintigraphy and ultrasonography, for the preoperative localization of parathyroid lesions in primary hyperparathyroidism.MethodsFifty-one patients cured after surgery were studied. Pinhole SPECT was reconstructed with a dedicated OSEM algorithm. Scintigraphies were analyzed visually. A diagnostic confidence score (CS) was assigned to each procedure considering intensity and extrathyroidal location of suspected lesions and was defined as follows: 0 = negative, 1 = doubtful, 2 = moderately positive, 3 = positive.ResultsSurgery revealed 55 lesions. Sensitivity of ultrasonography, planar imaging, conventional SPECT and pinhole SPECT were respectively, 51, 76, 82 and 87%. Five glands were only detected by pinhole SPECT. Combination of ultrasonography, planar and pinhole SPECT showed the highest sensitivity (94.5%). The mean CS of the 55 pathologic glands was significantly higher with pinhole SPECT compared with planar imaging and conventional SPECT (p < 0.0001). Compared with planar imaging and conventional SPECT, pinhole SPECT increased CS for 42 and 53% of parathyroid lesions, respectively, and contributed to markedly reduce the number of uncertain results. Nevertheless, planar imaging and ultrasonography were useful to analyze thyroid morphology and to detect some ectopic glands.ConclusionThe use of pinhole SPECT increases sensitivity and CS of scintigraphy. Combination of ultrasonography, planar and pinhole SPECT appears the optimal preoperative imaging procedure in primary hyperparathyroidism.     

Adding Rapid-Acting Insulin or Glp-1 Receptor Agonist to Basal Insulin: Outcomes in A Community Setting

ObjectiveTo evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist.MethodsData were extracted retrospectively from a U.S. health claims database. Adults with T2DM on basal insulin who added an RAI (basal + RAI) or GLP-1 receptor agonist (basal + GLP-1) were included. Propensity score matching (with a 1 up to 3 ratio) was used to control for differences in baseline demographics, clinical characteristics, and health resource utilization. Endpoints included prevalence of hypoglycemia, pancreatic events, all-cause and diabetes-related resource utilization, and costs at 1-year follow-up.ResultsOverall, 6,718 matched patients were included: 5,013 basal + RAI and 1,705 basal + GLP1. Patients in both groups experienced a similar proportion of any hypoglycemic event (P = .4079). Hypoglycemic events leading to hospitalization were higher in the basal + RAI cohort (2.7% vs. 1.8%; P = .0444). The basal + GLP-1 cohort experienced fewer all-cause (13.55% vs. 18.61%; P < .0001) and diabetes-related hospitalizations (11.79% vs. 15.68%; P < .0001). The basal + GLP-1 cohort had lower total all-cause health care costs ($18,413 vs. $20,821; P = .0002) but similar diabetes-related costs ($9,134 vs. $8,985; P < .0001) compared with the basal + RAI cohort.ConclusionsAdd-on therapy with a GLP-1 receptor agonist in T2DM patients receiving basal insulin was associated with fewer hospitalizations and lower total all-cause costs compared with add-on therapy using an RAI and could be considered as an alternative to an RAI in certain patients with T2DM who do not achieve effective glycemic control with basal insulin. (Endocr Pract. 2015; 21:68-76)     

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)     

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)     

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)     

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.     

HRPT2- (CDC73) Related Hereditary Hyperparathyroidism: A Case Series From Western India

Objective: To describe a case series of HRPT2- (CDC73) related hereditary primary hyperparathyroidism (PHPT) from western India.Methods: We present a case series of 4 families (7 patients) with PHPT caused by CDC73 gene mutations.Results: The mean age of presentation of the 4 index cases was 27.25 ± 9.8 years. Two family members were identified through biochemical screening (Cases 1b and 2b), while 1 mutation-positive family member did not manifest any features of PHPT or hyperparathyroidism jaw tumor syndrome (HPT-JT) syndrome (Case 2c). Biochemistry showed increased serum calcium (mean: 13.21 ± 1.24 mg/dL), low serum phosphorus (mean: 1.78 ± 0.44 mg/dL), and high parathyroid hormone (PTH, mean: 936 ± 586.9 pg/mL).All patients had a uniglandular presentation and underwent single adenoma excision initially except Cases 2a and 2b, who underwent subtotal parathyroidectomy at baseline. Two cases experienced PHPT recurrence (Cases 3 and 4), while 1 remained uncured due to parathyroid carcinoma (Case 1a). Other associated syndromic features like ossifying jaw fibromas were present in 2 patients, renal cysts in 3 patients, and uterine involvement in 2 patients. Two families had novel germline CDC73 mutations (Families 1 and 3), while the other 2 had reported mutations. Family 2 had familial isolated PHPT without any other features of HPT-JT syndrome.Conclusion: Our findings reaffirm the need for genetic analysis of patients with PHPT, especially those with younger age of disease onset; recurrent disease; and associated features like polycystic kidneys, endometrial involvement, ossifying jaw tumors, or parathyroid carcinoma.Abbreviations: FIHP = familial isolated hyperparathyroidism HPT-JT = hyperparathyroidism jaw tumor syndrome PHPT = primary hyperparathyroidism PTH = parathyroid hormone ⁹⁹Tc = ⁹⁹Technetium     

La concentration plasmatique de PTH permet-elle de sélectionner les patients atteints d’hyperparathyroïdie secondaire pour bénéficier de la scintigraphie double isotope MIBI (99mTc)/123I préopératoire ?

The utility of preoperative scintigraphy in case of secondary hyperparathyroidism is questioned by some authors. Obviously, an imaging modality that will detect all hyperplastic glands, including the ectopic ones, would be of interest in those patients at high risk for surgery. However, scintigraphy has a limited detection rate in some patients. We investigated whether one of the following parameters would identify a subgroup of patients in whom the detection rate would be optimal: age, gender, hemodialysis and duration since its onset, and plasma levels of parathyrin (PTH).MethodsRetrospective series of 38 patients referred for preoperative parathyroid scintigraphy due to secondary hyperparathyroidism who then underwent parathyroidectomy. Scintigraphy was performed 20 min and then 3 h after injection of 8 MBq/kg of sestamibi (^99mTc) with a previous ingestion of 0.1 MBq/kg iodine-123, 3 h before.ResultNo significant correlation was observed between the number of glands detected on scintigraphy (and confirmed by postoperative histology) and plasma PTH levels (r = ?0.17). A weak positive correlation (r = +0.34) was noted in the group of six non-hemodialysed patients. No significant relationship between this number of detected glands and a clinical parameter was observed.ConclusionIn our experience, these parameters do not permit to select, among patients with secondary hyperparathyroidism and scheduled for parathyroidectomy, those who will better benefit from parathyroid scintigraphy.     

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.     

Diagnosis by Serendipity: Cushing Syndrome Attributable to Cortisol-Producing Adrenal Adenoma as the Initial Manifestation of Multiple Endocrine Neoplasia Type 1 Due to a Rare Splicing Site Men1 Gene Mutation

ObjectiveTo report a case that highlights the potential for Cushing syndrome to be the first manifestation of multiple endocrine neoplasia type 1 (MEN 1) syndrome and to describe the rare underlying genetic mutation and the heterogeneous manifestations of the syndrome within the same family.MethodsWe present a case report including biochemical and radiologic findings, review family data, and discuss the results of genetic analyses.ResultsA 16-year-old girl who was not known to have any medical illness and had no known family history of MEN 1 syndrome presented with Cushing syndrome attributable to a cortisol-producing adrenal adenoma. During her evaluation, she was found to have primary hyperparathyroidism and a pituitary microprolactinoma. These findings raised the possibility of MEN 1 syndrome. She did not have clinical, biochemical, or radiologic evidence of islet cell pancreatic tumors. Family screening showed that her father had evidence of primary hyperparathyroidism, mild hyperprolactinemia, normal findings on magnetic resonance imaging of the pituitary, and a 1.2- cm nodule in the tail of the pancreas in conjunction with slight elevation of serum insulin and normal gastrin levels. The patient’s 5 siblings had evidence of primary hyperparathyroidism, and 2 of them also had mild hyperprolactinemia. Genetic screening confirmed the presence of a MEN1 gene missense G to A mutation in the patient, her father, and her siblings at the splicing site of intron 6 (IVS6 + 1G > A). This mutation leads to frameshift and truncation of the MEN1 gene.ConclusionIn MEN 1, Cushing syndrome is an extremely rare and usually late manifestation. Most cases are due to corticotropin-producing pituitary adenomas. Although Cushing syndrome generally develops years after the more typical manifestations of MEN 1 appear, it may be the primary manifestation of MEN 1 syndrome. There is considerable heterogeneity in the manifestations of MEN 1, even within a family having the same genetic mutation. (Endocr Pract. 2008;14:595-602)