RESEARCH DESIGN AND METHODS: 71 children with diabetes mellitus (43 diagnosed before 6 months of age, and 28 diagnosed between 6 months and 3 years of age who were negative for diabetes-associated autoantibodies) underwent genetic testing with a combination strategy of Sanger sequencing, chromosome microarray analysis and whole exome sequencing. They were categorized into four groups according to the age of onset of diabetes (at or less than 6 months, 6 to 12 months, 1 to 2 years, 2 to 3 years) to investigate the correlation between genotype and phenotype.
RESULTS: Genetic abnormalities were identified in 39 of 71 patients (54.93%), namely KCNJ11 (22), ABCC8 (3), GCK (3), INS (3), BSCL2 (1) and chromosome abnormalities (7). The majority (81.40%, 35/43) of neonatal diabetes diagnosed less than 6 months of age and 33.33% (3/9) of infantile cases diagnosed between 6 and 12 months of age had a genetic cause identified. Only 11.11% (1/9) of cases diagnosed between 2 and 3 years of age were found to have a genetic cause, and none of the 10 patients diagnosed between 1 and 2 years had a positive result in the genetic analysis. Vast majority or 90.48% (19/21) of patients with KCNJ11 (19) or ABCC8 (2) variants had successful switch trial from insulin to oral sulfonylurea.
CONCLUSIONS: This study suggests that genetic testing should be given priority in diabetes cases diagnosed before 6 months of age, as well as those diagnosed between 6 and 12 months of age who were negative for diabetes-associated autoantibodies. This study also indicates significant impact on therapy with genetic cause confirmation.
METHODS: Two reviewers searched MEDLINE for studies of ≥12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas.
RESULTS: Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%).
CONCLUSION: Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower.
MATERIALS AND METHODS: In this up to 33-week, open-label, active-controlled, parallel-group trial, adults [glycated haemoglobin (HbA1c) 7%-10% (53-86 mmol/mol); body mass index ≥20 kg/m(2) ; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once-daily liraglutide (final dose 1.8 mg) or continue pre-trial sulphonylurea at maximum tolerated dose, both with metformin.
PRIMARY ENDPOINT: change in fructosamine, a validated marker of short-term glycaemic control, during Ramadan.
RESULTS: Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (-12.8 µmol/L); sulphonylurea (-16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: -5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide-treated (2%, three subjects) versus sulphonylurea-treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: -0.54 kg; 95% CI: -0.94;-0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: -0.59% (-6.40 mmol/mol), 95% CI: -0.79; -0.38%; -8.63; -4.17 mmol/mol; p
Methods: A systematic search using predefined search terms in three scholarly databases, ScienceDirect, Google Scholar, and PubMed, was conducted. Original research articles published in the English language between 2012 and 2020 that reported renal outcomes associated with the use of non-insulin AD pharmacotherapy were eligible for inclusion. Review articles, meta-analysis studies, and conference proceedings were excluded. A study-specific data extraction form was designed to extract the author's name, country, publication year, study design, study population, objectives, key findings, and conclusions. A narrative review of the key findings that focused on renal outcomes and renal safety issues was conducted.
Results: Of the 18,872 results identified through the initial search, a total of 32 articles were included in this review. Of these, 18 of the included articles reported the renal outcomes of newer antidiabetic medications, eg, SGLT2 inhibitors and GLP-1 agonists. Eight studies focussed on the well-established antidiabetic medications, eg, metformin and sulphonylureas. The review reported three main types of the clinical impact of the prescribed AD on the renal outcomes: "renoprotective effects", "no additional risk" and "associated with a decline in renal parameters". Seventeen studies reported the renoprotective effects of AD, including SGLT2i studies (n=8), GLP1 studies (n=6), and DPP4i studies (n=3). The reported renoprotective effects included slowing down the GFR decline, improving albuminuria, and reducing renal adverse events. The "no additional risk" impact was reported in eight studies, including DPP4i studies (n=3), two SGLT2i studies (n=2), metformin studies (n=2), and one study involving pioglitazone. Furthermore, seven studies highlighted the "associated with a decline in renal parameters" effect. Of these, three involved SGLT2i, two with metformin, and one for each DPP4i and sulphonylurea.
Conclusion: More than half of the studies included in this review supported the renoprotective effects associated with the use of AD medications, particularly GLP-1A, SGLT2i, and some of the DPP4i. Further studies involving patients with various stages of chronic kidney disease (CKD) are required to compare AD medications' renal effects, particularly the newer agents.