[Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus]. / Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2.

Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial.

In this post hoc analysis of the randomized controlled LixiLan-O trial in insulin-naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed-ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs.

Efficacy and Safety of Canagliflozin in Type 2 Diabetes Patients of Different Ethnicity.

OBJECTIVE: To assess the efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin in patients of different ethnicities. DESIGN SETTING AND PATIENTS: Post hoc analysis of data pooled from four randomized, placebo-controlled, phase 3 studies of adults with inadequately controlled type 2 diabetes mellitus (T2DM). INTERVENTIONS: Once daily oral canagliflozin 100 mg or 300 mg, or placebo. MAIN OUTCOME MEASURES: Efficacy endpoints included change from baseline in HbA1c, body weight (BW), systolic blood pressure (SBP), and lipids at week 26; safety and tolerability were assessed by adverse event reports. RESULTS: Of the 2,313 patients included in this pooled analysis, 609 self-identified as Hispanic/Latino. Hispanic/Latino patients had a mean age of 54 years, mean duration of T2DM of 7 years, mean HbA1c of 8.1%, mean body mass index of 31.2 kg/m(2), and mean SBP of 126.1 mm Hg. There were more women in the non-Hispanic/Latino cohort (63%) compared with the Hispanic/Latino cohort. Placebo-subtracted changes in HbA1c were -.82% with canagliflozin 100 mg and -.94% with canagliflozin 300 mg in the Hispanic/Latino cohort, which were similar to reductions observed in the non-Hispanic/Latino cohort. Significantly greater dose-related reductions in HbA1c, BW, and SBP were observed with both canagliflozin doses compared with placebo. Canagliflozin was generally well-tolerated. Genital mycotic infections were less frequent in Hispanic/Latino women than in non-Hispanic/Latino women. CONCLUSIONS: The SGLT2 inhibitor canagliflozin was generally well-tolerated and was associated with clinically meaningful reductions in HbA1c, BW, and SBP in both Hispanic/Latino and non-Hispanic/Latino patients with T2DM.

The treatment of diabetes mellitus of patients with chronic liver disease.

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.

Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study.

AIMS: To define if there is an imbalance in plasma levels of proinflammatory, fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and impaired glucose tolerance (IGT) or diabetes mellitus (DM). MATERIAL AND METHODS: We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma levels of cytokines were measured: TNF- α, soluble tumor necrosis factor receptor 1 (sTNF-R1), leptin, TGF-ß1, and hepatocyte growth factor (HGF). Also, fasting plasma insulin (FPI) levels were determined and HOMA2-IR was calculated. Results were compared with those of a control group of 18 patients without liver disease nor DM. Intergroup comparison was performed using non parametric tests. RESULTS: Significantly higher sTNF-R1 and lower TGF-ß1 were found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF-α levels showed no significant differences. According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found. CONCLUSIONS: IGT and DM were associated with abnormalities of sTNF-R1 and TGF-ß1 compared to non cirrhotic controls. Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease. Finally, sTNF-R1 and leptin correlated with IR. These findings suggest that IGT and DM may be causally implicated with liver inflammation process.

Type 2 diabetes in latin America: recommendations on the flash glucose monitoring system.

OBJECTIVE: To establish recommendations through the consensus of a Latin American experts panel on the use of the flash glucose monitoring system (fCGM) in people living with type 2 diabetes mellitus (T2DM) regarding the benefits and challenges of using the fCGM. METHODS: An executive committee of experts was created, comprised by a panel of fifteen physicians, including endocrinologists and internal medicine physicians, with expertise in management of adult patients with T2DM. The experts were from various countries: Colombia, Chile, Peru, Mexico, Argentina, and Brazil. The modified Delphi method was used, considering a consensus level of at least 80% of the participants. A seventeen-item instrument was developed to establish recommendations on the use of fCGM in patients with T2DM in Latin American. RESULTS: The number of glucose scans recommended per day with the fCGM for patients managed with oral antidiabetic drugs or basal insulin was a median of 6 scans per day, and for those managed with multiple insulin doses, a median of 10 scans per day was recommended. Additionally, a holistic and individualized management approach was recommended, taking into account new treatment directions and identifying patients who would benefit from the use of the fCGM. CONCLUSION: Continuous use of the fCGM is recommended for people living with T2DM, regardless of their type of treatment. These metrics must be evaluated individually for each patient profile.

[Diabetes in liver cirrhosis]. / La diabetes en la cirrosis hepática.

The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes¼. Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease.

A review of flash glucose monitoring in type 2 diabetes.

BACKGROUND: Continuous glucose monitoring systems are increasingly being adopted as an alternative to self-monitoring of blood glucose (SMBG) by persons with diabetes mellitus receiving insulin therapy. MAIN BODY: The FreeStyle Libre flash glucose monitoring system (Abbott Diabetes Care, Witney, United Kingdom) consists of a factory-calibrated sensor worn on the back of the arm which measures glucose levels in the interstitial fluid every minute and stores the reading automatically every 15 min. Swiping the reader device over the sensor retrieves stored data and displays current interstitial glucose levels, a glucose trend arrow, and a graph of glucose readings over the preceding 8 h. In patients with type 2 diabetes (T2D) receiving insulin therapy, pivotal efficacy data were provided by the 6-month REPLACE randomized controlled trial (RCT) and 6-month extension study. Compared to SMBG, the flash system significantly reduced the time spent in hypoglycemia and frequency of hypoglycemic events, although no significant change was observed in glycosylated hemoglobin (HbA1c) levels. Subsequent RCTs and real-world chart review studies have since shown that flash glucose monitoring significantly reduces HbA1c from baseline. Real-world studies in both type 1 diabetes or T2D populations also showed that flash glucose monitoring improved glycemic control. Higher (versus lower) scanning frequency was associated with significantly greater reductions in HbA1c and significant improvements in other measures such as time spent in hypoglycemia, time spent in hyperglycemia, and time in range. Additional benefits associated with flash glucose monitoring versus SMBG include reductions in acute diabetes events, all-cause hospitalizations and hospitalized ketoacidosis episodes; improved well-being and decreased disease burden; and greater treatment satisfaction. CONCLUSION: T2D patients who use flash glucose monitoring might expect to achieve significant improvement in HbA1c and glycemic parameters and several associated benefits.

Gestational diabetes mellitus and COVID-19, clinical characteristics and review of the literature.

There is a lack of information about the maternal-fetal outcomes in patients with gestational diabetes and concomitant COVID-19; and there is even less information about the outcomes of pregnant women with gestational diabetes and COVID-19. We present a case of a primigravidae of 20-year-old woman with gestational diabetes and COVID-19 and a review of the literature.

Vaspin, a Compensatory Mechanism Against High Glucose Levels Since Birth?

Objective: Hormones produced by fat tissue, adipokines, produced during intrauterine life have recently been implicated in fetal growth. Vaspin is an adipokine expressed in visceral adipose tissue and has insulin-sensitizing effects. Elevated serum vaspin concentrations are associated with alterations in insulin sensitivity. We aimed to determine if vaspin concentrations in cord blood from healthy, term newborns differ among those born small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). A secondary objective was to determine whether an association existed between vaspin and anthropometric measurements, glucose and insulin levels in the newborn. Methods: The study population included healthy term newborns, 30 subjects in the SGA, 12 in the AGA, and 34 in the LGA group. Anthropometry was documented in all subjects. Blood was taken from the umbilical cord vein from each child for later analysis for vaspin, insulin and glucose concentrations. Results: Cord blood vaspin, insulin and glucose concentrations were not different between the three study groups. A negative correlation between vaspin and glucose concentrations was demonstrated in the whole cohort (r=-0.364, p=0.001). This correlation was also observed in the LGA group (r=-0.482, p=0.004). Glucose concentrations significantly predicted vaspin concentrations (r2=0.132, p=0.001). Conclusion: We found a negative association between glucose and vaspin concentrations in umbilical cord blood. In addition there was a predictive association between blood glucose and resulting vaspin concentration, suggesting that vaspin can be used as a predictor of alterations in the insulin-glucose metabolism from birth.

Association of Patient Profile with Glycemic Control and Hypoglycemia with Insulin Glargine 300 U/mL in Type 2 Diabetes: A Post Hoc Patient-Level Meta-Analysis.

AIMS: To examine the association of baseline patient characteristics with study outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100), over a 6-month period. METHODS: A post hoc patient-level meta-analysis using data from three multicenter, randomized, open-label, parallel-group, phase 3a studies of similar design, in people previously receiving either basal and prandial insulin, basal insulin + oral antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively). The endpoints, glycated hemoglobin (HbA1c), hypoglycemia, body weight change, and insulin dose were investigated by subgroups: age (< 65 and ≥ 65 years), body mass index (BMI; < 30 and ≥ 30 kg/m2), age at onset (< 40, 40-50, and > 50 years), and diabetes duration (< 10 and ≥ 10 years). RESULTS: Reduction in HbA1c was comparable between insulins, regardless of subgroup. The lower risk of ≥ 1 nocturnal (00:00-05:59 h) confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant characteristics. While heterogeneity of treatment effect between diabetes duration subgroups was seen for the risk of ≥ 1 confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect consistently favored Gla-300; no evidence of heterogeneity was observed for the other subgroups. Annualized rates of confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia and body weight change were not influenced by participant characteristics; a similar pattern was observed with insulin dose. CONCLUSIONS: Comparable glycemic control was observed with Gla-300 versus Gla-100, with less hypoglycemia, regardless of age, BMI, age at onset or diabetes duration. FUNDING: Sanofi. Plain language summary available for this article.

Association between serum uric acid and metabolic syndrome components in prepubertal obese children (Tanner Stage I) from Nuevo León, Mexico - a preliminary study.

BACKGROUND: Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease and diabetes. Previous studies in obese children demonstrating a positive association between serum uric acid (sUA) and components of MetS are confounded by lack of uniformity in age and pubertal status of children. Therefore, we have examined the role of sUA in MetS and its components in pre-pubertal children (Tanner Stage I, age ≤ 9 years). METHODS: Pre-pubertal obese children (32 boys, 27 girls, age 6-9 years) were recruited from Nuevo Leon, Mexico. For comparison, an equal number of children with normal body mass index (BMI) in the same age range (22 Boys, 39 girls, age 6-9 years) were also recruited from the same community. Presence of MetS and its components was defined according to the criteria of International Diabetes Federation. Fasting blood was analyzed for lipids, glucose, insulin, and uric acid. RESULTS: Among the obese children, sUA was positively associated with insulin resistance and hypertriglyceridemia and negatively associated with high density lipoprotein-cholesterol (HDLc). Subjects were three times more likely to have a MetS diagnosis per one unit (md/dL) difference in sUA. Of the 59 obese pre-pubertal children, 20 were classified as having MetS defined by the presence of abdominal obesity and two or more of other components described under methods. Of these, 57.1% (20/61) had sUA between 5.1 and 7.1 mg/dl. CONCLUSIONS: The findings of this study clearly indicate a positive relationship between uric acid and MetS and its components in pre-pubertal obese children with Tanner stage I and ≤9 years of age.

Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2 / Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus

Resumen Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Abstract Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Patients' empowerment, physicians' perceptions, and achievement of therapeutic goals in patients with type 1 and type 2 diabetes mellitus in Mexico.

BACKGROUND: Physicians' perception may not parallel objective measures of therapeutic targets in patients with diabetes. This is an issue rarely addressed in the medical literature. We aimed to analyze physicians' perception and characteristics of adequate control of patients with diabetes. PATIENTS AND METHODS: We studied information on physicians and their patients who participated in the third wave of the International Diabetes Management Practices Study registry in Mexico. This analysis was performed on 2,642 patients, 203 with type 1 diabetes mellitus (T1DM) and 2,439 with type 2 diabetes mellitus (T2DM), treated by 200 physicians. RESULTS: The patients perceived at target had lower hemoglobin A1c (HbA1c) and fasting blood glucose than those considered not at target. However, overestimation of the frequency of patients with HbA1c <7% was 41.5% in patients with T1DM and 31.7% in patients with T2DM (underestimation: 2.8% and 8.0%, respectively). The agreement between the physicians' perception and the class of HbA1c was suboptimal (κ: 0.612). Diabetologists and endocrinologists tested HbA1c more frequently than primary care practitioners, internists, or cardiologists; however, no differences were observed in mean HbA1c, for both T1DM (8.4% vs 7.2%, P=0.42) and T2DM (8.03% vs 8.01%, P=0.87) patients. Nevertheless, insulin users perceived at target, who practiced self-monitoring and self-adjustment of insulin, had a lower mean HbA1c than patients without these characteristics (mean HbA1c in T1DM: 6.8% vs 9.6%, respectively; mean HbA1c in T2DM: 7.0% vs 10.1%, respectively). CONCLUSION: Although there is a significant physicians' overestimation about the optimal glycemic control, this global impression and characteristics of patients' empowerment, such as self-monitoring and self-adjustment of insulin, are associated with the achievement of targets.

Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America.

OBJECTIVE: This post hoc analysis evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) from Latin America. RESEARCH DESIGN AND METHODS: Analyses were performed in subgroups of patients from Latin America based on data from three individual, 26-week, placebo-controlled studies of canagliflozin (monotherapy [n = 116/584], add-on to metformin [n = 199/918], and add-on to metformin plus sulfonylurea [n = 76/469]) and three individual, 52-week, active-controlled studies of canagliflozin (add-on to metformin versus sitagliptin [n = 240/1101], add-on to metformin versus glimepiride [n = 155/1450], and add-on to metformin plus sulfonylurea versus sitagliptin [n = 156/755]). MAIN OUTCOME MEASURES: Changes from baseline in HbA1c, body weight, and systolic blood pressure (BP) with canagliflozin 100 and 300 mg versus placebo or active comparator (i.e., sitagliptin or glimepiride) were evaluated in the overall study populations and Latin American subgroups. Safety was assessed based on adverse event (AE) reports. RESULTS: Canagliflozin 100 and 300 mg provided reductions in HbA1c, body weight, and systolic BP across studies in patients from Latin America that were generally similar to those seen in the overall populations of patients with T2DM. The AE profile in patients from Latin America was equivalent to that in the overall populations; higher rates of genital mycotic infections and osmotic diuresis-related AEs were seen with canagliflozin versus comparators. Limitations of this study include the post hoc analysis of data and the small sample size of patients from Latin America. CONCLUSION: Canagliflozin improved glycemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM from Latin America. CLINICAL TRIAL REGISTRATION: NCT01081834; NCT01106677; NCT01106625; NCT00968812; NCT01137812.

Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.

OBJECTIVES: To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks. METHODS: Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c <0% and body weight <0 kg, and attainment of HbA1c <7.0% and body weight reduction ≥5% at Week 52 were evaluated. Safety was assessed based on adverse event reports. RESULTS: Canagliflozin provided reductions in HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c <7.0% and body weight reduction ≥5% with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (18.9%, 18.3%, and 5.7%, respectively). Canagliflozin was generally well tolerated. CONCLUSIONS: A greater proportion of patients with T2DM achieved reductions in both HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.

Severe Hypercalcaemia - Chronic Tophaceous Gout as the Responsible Cause?

The association of chronic tophaceous gout with severe hypercalcaemia is exceptional. In this case, a 42-year old man with a long-standing history of gout arrived at the emergency room with altered mental status. Laboratory work up revealed a uric acid of 14.0 mg/dl, corrected calcium of 14.5 mg/dl, phosphorous of 6.3 mg/dl, parathyroid hormone (PTH) was suppressed (<3.0 pg/ml), 25-dihydroxyvitamin D 25.2 ng/ml, parathyroid hormone related-protein (PTHrP) was 45.0 pg/ml and calcitriol 19.6 pg/ml. Biopsy histopathology result showed deposits of monosodium urate crystals surrounded by granulomatous inflammation. The association of chronic tophaceous gout with severe hypercalcaemia is extremely rare and has been usually described to be secondary to 1-25 dihydroxyvitamin D (calcitriol) secretion. In this case, calcitriol levels were normal and this possibility was excluded. On the other hand, PTHrP had never been, until now, described as the responsible cause of hypercalcaemia in gout. In our case, baseline PTHrP and calcium values were elevated and after medical treatment both returned to normal values. PTHrP usually causes hypophosphataemia and in this case the abnormal renal function could have diminished this last effect.

The biosimilar insulin landscape: current developments.

Biosimilar insulins have the potential to increase access to treatment among patients with diabetes mellitus, reduce treatment costs, and expand market competition. The patents for several insulins are soon to expire, meaning there is room for copies of these products--or 'biosimilars'--to join the marketplace. It is vital that similar safety and efficacy to the innovator product is demonstrated for biosimilars. This presents many possible manufacturing and regulatory challenges. Complex manufacturing processes mean that even small differences between manufacturers can have a potential impact on the final product. Several companies are currently developing biosimilar insulins or are already producing these products in emerging markets with different regulatory requirements. For insulin biosimilars to be licensed in more established markets, manufacturers will need to meet the rigid criteria set out by agencies such as the European Medicines Agency and US Food and Drug Administration, and fulfill several pre-clinical, clinical, and pharmacovigilance surveillance criteria. As a result of differing regulatory requirements, there are possible gaps in the publically available clinical data to support the safety and efficacy of biosimilar insulins from around the world current as of July 2014. This review summarizes the current biosimilar insulin landscape.

Safety and effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes switching from basal-bolus insulin regimens in the A1chieve study.

AIMS: Biphasic insulin aspart 30 allows fewer daily injections versus basal-bolus insulin regimens, which may improve adherence and treatment outcome. This sub-analysis of the observational A1chieve study assessed clinical safety and effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes previously receiving basal-bolus insulin regimens. METHODS: A1chieve was an international, open-label, 24-week study in people with type 2 diabetes starting/switching to biphasic insulin aspart 30, insulin detemir or insulin aspart. This sub-analysis assessed patients switching from insulin glargine- or neutral protamine Hagedorn insulin-based basal-bolus insulin regimens to biphasic insulin aspart 30. RESULTS: 1024 patients were included. At 24 weeks, glycated haemoglobin and fasting plasma glucose were significantly reduced from baseline in both cohorts (all p<0.001). The proportion reporting any hypoglycaemia, major hypoglycaemia or nocturnal hypoglycaemia was significantly reduced after 24 weeks (all p<0.05). No serious adverse drug reactions were reported. Both cohorts had significantly improved health-related quality of life (HRQoL; p<0.001). CONCLUSIONS: 24 weeks after switching from basal-bolus insulin regimens to biphasic insulin aspart 30, glycaemic control and HRQoL were significantly improved, and hypoglycaemia was significantly reduced. This suggests that people with type 2 diabetes inadequately controlled on basal-bolus insulin regimens can consider biphasic insulin aspart 30.