scholarly journals P44 Type 2 diabetes mellitus in children: non-insulin medication, where are we up to?

2019 ◽  
Vol 104 (6) ◽  
pp. e35.2-e35
Author(s):  
R Austin ◽  
P Paul ◽  
D Hawcutt

BackgroundChildhood type 2 diabetes mellitus (T2DM) is a relatively rare condition but is an important health concern as its prevalence continues to rise. Current management consists of lifestyle modification, metformin and insulin. Several new pharmacological classes are currently used in adult medicine but are not yet available in paediatric care.In this review we will look at the current evidence for use of these newer medications in the paediatric population.MethodsA literature search (EMBASE, Medline, Pubmed, CINHAL) was performed for papers studying the use of non-insulin medications in children; including a separate search of ´clinicaltrials.gov´ to identify any ongoing trials in paediatric T2DM.ResultsNewer classes of medications include incretin mimetics, dipeptidyl peptidase-4-inhibitors, sodium/glucose-cotransporter-2-inhibitors, and thiazolidinediones. There have been a small number of pharmacokinetic/pharmacodynamic studies carried out in small cohorts of paediatric participants, but larger long-term efficacy and safety trials are lacking. These studies and individual case-reports have shown good tolerability but are unable to identify any long-term effects associated with these medications.Randomised controlled trials studying rosiglitazone and glimepiride use in children have been performed. However, safety concerns in adults and notable side-effects including weight gain, mean their future use is uncertain.Currently many relevant trials involving paediatric patients listed on ´clinicaltrials.gov´ are awaiting completion.ConclusionMedical management for T2DM in children remains limited. Ongoing studies are aiming to equip practitioners with wider treatment options in the future. However, there are concerns regarding the long-term safety of these medications due to the increased risk of pancreatitis, gallbladder conditions and bladder malignancy in adult patients.Paediatric T2DM patients suffer from complications earlier and more severely compared with adults, making this is a pressing issue. Long-term surveillance studies to identify adverse effects and a framework for highlighting research gaps are required to enable improvements in paediatric T2DM management.Disclosure(s)Nothing to disclose

2017 ◽  
Vol 32 (2) ◽  
pp. 240-243 ◽  
Author(s):  
Ryan B. Dull ◽  
Mikayla L. Spangler ◽  
Emily L. Knezevich ◽  
Britney M. Lau

Introduction and Objective: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium–glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. Case Reports: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin. This case was notable for a delayed diagnosis of euDKA and lack of clinical improvement despite withholding dapagliflozin. Subject 2 is a 62-year-old male admitted with euDKA precipitated by infection. His clinical condition improved rapidly and euDKA responded to withdrawal of empagliflozin alone. Discussion: Applying the Naranjo adverse medication reaction probability scale to each case (subject 1 score = 3 points; subject 2 score = 4 points) suggests these are possible adverse reactions to SGLT2i. Data from randomized controlled trials suggest DKA events in adults with type 2 DM receiving SGLT2i are rare and similar to placebo. However, data from a large cohort suggest these events occur more frequently and are associated with a 2-fold increased risk of DKA. Conclusion: This class of medications may be associated with a higher real-world risk of DKA in adults with type 2 DM than previously reported. Patients prescribed these medications should receive vigilant assessment for features of traditional DKA as well as euDKA.


2020 ◽  
Vol 8 (1) ◽  
pp. e001346
Author(s):  
Carlos K H Wong ◽  
Kenneth K C Man ◽  
Esther W Y Chan ◽  
Tingting Wu ◽  
Emily T Y Tse ◽  
...  

IntroductionThis study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin–sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.Research design and methodsWe assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin–sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.ResultsOver a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p<0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively.ConclusionsFor patients with T2DM on metformin–sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.


2020 ◽  
Author(s):  
Nobuko Kitagawa ◽  
NORIYUKI KITAGAWA ◽  
Emi Ushigome ◽  
Hidetaka Ushigome ◽  
Isao Yokota ◽  
...  

Abstract Background A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy. However, this association has not been previously assessed over medium to long term. Methods This prospective 5-year cohort study of 424 patients with normoalbuminuria investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as advancement from normoalbuminuira to micro- or macroalbuminuria. Results Among 424 patients, 75 developed diabetic nephropathy during the study period. Adjusted odds ratio of developing diabetic nephropathy because of IH-HSBP was 2.39 (95% confidence interval 1.15–4.96, p = 0.02). Sex; body mass index; duration of diabetes mellitus; and levels of hemoglobin A1c, total cholesterol, creatinine; and use of renin-angiotensin-aldosterone system inhibitors were included in the model as covariates. Conclusions IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normoalbuminuria over medium to long term. These findings suggest that IH-HSBP might be a useful marker in disease prognostication.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1129-P
Author(s):  
SILVINA GALLO ◽  
BERNARD CHARBONNEL ◽  
ALLISON GOLDMAN ◽  
HARRY SHI ◽  
SUSAN HUYCK ◽  
...  

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


2020 ◽  
Vol 16 ◽  
Author(s):  
Patricio Lopez-Jaramillo ◽  
Jose Lopez-Lopez ◽  
Daniel Cohen ◽  
Natalia Alarcon-Ariza ◽  
Margarita Mogollon-Zehr

: Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and near to 40% are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has been also associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus represent a substantial cost for the weak health systems of Latin American countries. Therefore, is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the Unit Nations of decrease the premature mortality for CVD.


2020 ◽  
Vol 15 ◽  
Author(s):  
Jim Philip ◽  
Cornelius James Fernandez

: Meglitinides are a group of oral hypoglycemic medications currently approved for the treatment of type 2 diabetes mellitus (T2DM). Two meglitinide molecules, Repaglinide and Nateglinide,are presently in use. Repaglinide is preferred because of its superior glycemic efficacy.They have modest efficacy with a mean decrement of glycosylated haemoglobin (HbA1c) ranging between -0.2 to -1.50% with individual therapy. Additional HbA1c reduction can occur with combination therapy with other oral hypoglycemics. This class of drugs is effective in controlling postprandial hyperglycemia with minimal risk of hypoglycemia.It is also useful in patients in with variable meal timings, especially in the elderly, and in patients with renal failure. There are is a dearth of long-term studies on meglitinides to assess cardiovascular outcomes or mortality in T2DM,although the Nateglinide and Valsartan in Impaired Glucose ToleranceOutcomes Research (NAVIGATOR) study showed no difference between Nateglinide and placebo with regard to the core composite cardiovascular outcomes. Based on a PubMed literature search using key words: ‘meglitinides’, ‘repaglinide’, ‘nateglinide’, ‘HbA1c’, ‘glycated haemoglobin’, ‘cardiovascular safety’, ‘cardiovascular events’, ‘cardiovascular outcome trials’, ‘type 2 diabetes mellitus’ and heart failure, and combining the search terms using Boolean operators ‘AND’, ‘OR’ and ‘NOT’ as needed we compiled current evidence for use of these oral hypoglycemic agents in clinical use. This article is an attempt to review the efficacy and cardiovascular (CV) safety of Meglitinides to help clinicians to use this class of oral hypoglycaemic agents prudently.


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