To assess the association between insulin regimens and health-related quality of life (HRQoL) after the introduction of basal insulin (BI) among people with type 2 diabetes in real-world clinical settings. 16,339 registered people with diabetes who had inadequate glycaemic control by oral agents initiated BI (either single BI or Basal-bolus) and completed a 6-month follow-up from 209 hospitals were included in the analyses. At the end of the follow-up, the switches of insulin regimens, change of HRQoL (EQ-5D-3L) and their associations were assessed. Initial insulin regimens of single BI and of basal-bolus (BI included Glargine, Detemir, and Neutral Protamine Hagedorn) accounted for 75.6% and 24.4%, respectively. At 6 months, regimens used were BI alone (65.2%), basal-bolus (10.4%), and premixed (6.4%), whereas 17.9% stopped all insulin therapy. The visual analogue scale score increased by 5.46 (P < .001), and the index value increased slightly by 0.02 (P < .001). Univariate analysis showed that people with diabetes taking basal-bolus regimen had the greatest improvement on HRQoL in all dimensions, especially in the reduction of the percentage of Pain/Discomfort (by 10.03%) and Anxiety/Depression (by 11.21%). In multivariable analysis, single BI or premixed insulin at 6 months was associated with more improvement of visual analogue scale score compared with stopping all insulin. Improved HRQoL was observed after initiating BI in people with type 2 diabetes . If the same achievement on HbA1c control can be guaranteed, single BI is preferred to other regimens from the viewpoint of HRQoL. Basal-bolus has the most significant potential to increase HRQoL, however, the people with diabetes characteristics differ from those initiating BI alone. Further longitudinal cohort study with a longer study period might be necessary to evaluate the certain effect.
Obesity is one of the most important risk factors for type 2 diabetes (T2D). The aim of this study is to examine the associations between established obesity-related genomic loci and T2D as well as multiple quantitative glycemic traits among Chinese population. Single nucleotide polymorphisms (SNPs) near or within genes NEGR1 , SEC16B , TMEM18 , ETV5/DGKG , BAT2 , BDNFOS , BDNF , FAIM2 , MC4R , KCTD15 , MTCH2 , GNPDA2 , NPC1 , MAF , PTER , PRL , PCSK1 , PFKP , CTNNBL1 , NRXN3 , MSRA , SLC30A10 and TFAP2B from 23 independent genomic loci were genotyped among 5,338 T2D patients and 4,663 controls. An additive genetic model was assumed. Logistic and linear regression models were used to examine the associations of these genomic loci with T2D and glycemic traits, respectively. Two SNPs near MC4R (rs12970134) and GNPDA2 (rs10938397) genes were significantly associated with T2D after adjusting for age and gender (OR [95% CI] = 1.14 [1.06, 1.22] for per A allele of rs12970134, P = 4.75х10 -4 ; OR [95% CI] = 1.10 [1.03, 1.17] for per G allele of rs10938397, P = 4.54х10 -3 ). When body mass index (BMI) and waist circumference was further adjusted for in logistic regression models, the association of MC4R with T2D maintained significant (OR [95% CI] = 1.10 [1.02, 1.20], P = 1.81х10 -2 ) and that of GNPDA2 attenuated to non-significance (OR [95% CI] = 1.06 [0.98, 1.14], P = 1.26х10 -1 ). In addition, eight loci (near or within SEC16B , BDNF , KCTD15 , MAF , PRL , PCSK1 , CTNNBL1 and NRXN3 genes) showed significant associations with quantitative glycemic traits in the controls even after adjusting for BMI and waist circumference ( P < 0.05). For example, the G allele of SNP rs10146997 in the NRXN3 gene was associated with higher fasting insulin level (β [SE] = 0.064 [0.026], P = 1.31х10 -2 ), HOMA-IR (β [SE] = 0.064 [0.027], P = 1.71х10 -2 ) and lower insulin sensitivity (assessed by Matsuda index, β [SE] = -0.051 [0.026], P = 4.67х10 -2 ) compared to the A allele. The T allele of SNP rs6013029 in the CTNNBL1 was associated with greater fasting insulin(β [SE] = 0.098 [0.038], P = 1.02х10 -2 ), HOMA-IR (β [SE] = 0.100 [0.039], P = 1.13х10 -2 ) and HOMA-B (β [SE] = 0.104 [0.053], P = 4.73х10 -2 ), as well as lower insulin sensitivity (β [SE] = -0.096 [0.039], P = 1.47х10 -2 ) compared to G allele, suggesting its potential role in insulin resistance. In conclusion, these data suggest that these obesity-related genomic loci may be associated with T2D and glycemic traits after accounting for BMI and waist circumference among Chinese population.
Abstract Aim To evaluate the efficacy and safety of once‐weekly subcutaneous semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes (T2D) in a multiregional clinical trial. Materials and Methods In the 30‐week, randomized, double‐blind, double‐dummy, active comparator SUSTAIN China trial, 868 adults with T2D inadequately controlled on metformin (HbA1c 7.0%‐10.5%) were randomized to receive once‐weekly semaglutide 0.5 mg (n = 288), semaglutide 1.0 mg (n = 290) or once‐daily sitagliptin 100 mg (n = 290). The primary and confirmatory secondary endpoints were change from baseline to week 30 in HbA 1c and body weight, respectively. Results The trial enrolled ~70% (605/868) of the patients in China, and the remaining patients from four other countries, including the Republic of Korea. Both doses of semaglutide were superior to sitagliptin in reducing HbA 1c and body weight after 30 weeks of treatment. The odds of achieving target HbA 1c of less than 7.0% (53 mmol/mol), weight loss of 5% or higher, or 10% or higher, and the composite endpoint of HbA 1c less than 7.0% (53 mmol/mol) without severe or blood glucose‐confirmed symptomatic hypoglycaemia no weight gain, were all significantly higher with both semaglutide doses compared with sitagliptin. The safety profile for semaglutide was consistent with the known class effects of GLP‐1 receptor agonists (RAs). Consistent efficacy and safety findings were seen in the Chinese subpopulation. Conclusions Once‐weekly semaglutide was superior to sitagliptin in improving glycaemic control and reducing body weight in patients with T2D inadequately controlled on metformin. The safety and tolerability profiles were consistent with those of semaglutide and other GLP‐1 RAs. Semaglutide is an effective once‐weekly treatment option for the Chinese population.
With the growing prevalence of type 2 diabetes, particularly in emerging countries, its management in the context of available resources should be considered. International guidelines, while comprehensive and scientifically valid, may not be appropriate for regions such as Asia, Latin America or Africa, where epidemiology, patient phenotypes, cultural conditions and socioeconomic status are different from America and Europe. Although glycaemic control and reduction of micro- and macrovascular outcomes remain essential aspects of treatment, access and cost are major limiting factors; therefore, a pragmatic approach is required in restricted-resource settings. Newer agents, such as sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in particular, are relatively expensive, with limited availability despite potentially being valuable for patients with insulin resistance and cardiovascular complications. This review makes a case for the role of more accessible second-line treatments with long-established efficacy and affordability, such as sulfonylureas, in the management of type 2 diabetes, particularly in developing or restricted-resource countries.
The Global Partnership for Effective Diabetes Management, established to provide practical guidance to improve patient outcomes in diabetes, has developed and modified recommendations to improve glycaemic control in type 2 diabetes. The Global Partnership advocates an individualized therapeutic approach and, as part of the process to customize therapy, has previously identified specific type 2 diabetes patient subgroups that require special consideration. This article builds on earlier publications, expanding the scope of practical guidance to include newly diagnosed individuals with complications and women with diabetes in pregnancy. Good glycaemic control remains the cornerstone of managing type 2 diabetes, and plays a vital role in preventing or delaying the onset and progression of diabetic complications. Individualizing therapeutic goals and treatments to meet glycaemic targets safely and without delay remains paramount, in addition to a wider programme of care to reduce cardiovascular risk factors and improve patient outcomes.
To evaluate the efficacy and safety of janagliflozin, a selective renal sodium-glucose cotransporter-2 inhibitor, as monotherapy in drug-naive Chinese patients with type 2 diabetes mellitus (T2DM).This Phase 3 trial included a 24-week, multicentre, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. A total of 432 patients with glycated haemoglobin (HbA1c) levels ≥7.0% (53 mmol/mol) and ≤10.5% (91 mmol/mol) were randomized (1:1:1) to receive once-daily placebo, 25 mg or 50 mg janagliflozin. After 24 weeks, patients on placebo were switched and re-randomized (1:1) to 25 mg or 50 mg janagliflozin, whereas patients on janagliflozin maintained the initial therapy. The primary endpoint was change from baseline in HbA1c after 24 weeks.At Week 24, the placebo-adjusted least squares mean changes in HbA1c were -0.80% (95% confidence interval [CI] -0.98% to -0.62%)/-8.7 mmol/mol (95% CI -10.7 mmol/mol to -6.8 mmol/mol) and -0.88% (95% CI -1.06% to -0.70%)/-9.6 mmol/mol (95% CI -11.6 mmol/mol to -7.7 mmol/mol), respectively (P < 0.001 for both). A higher proportion of patients achieved HbA1c <7.0% (53 mmol/mol) with janagliflozin 25 mg and janagliflozin 50 mg compared with placebo (47.2%, 49.3%, and 23.5%, respectively). Both janagliflozin doses significantly decreased fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, as well as increased high-density lipoprotein (HDL) cholesterol and insulin sensitivity compared with placebo (P < 0.05 for all). The trends in improvement of these variables were sustained during the 28-week extension period. Overall incidences of adverse events were 67.8%, 71.5% and 60.7% with janagliflozin 25 mg, janagliflozin 50 mg and placebo, respectively. The incidence of urinary tract infections and genital fungal infections was low. No severe hypoglycaemia or ketoacidosis occurred.Janagliflozin 25 mg and 50 mg monotherapy once-daily effectively improved glycaemic control, reduced body weight and blood pressure, improved HDL cholesterol and insulin sensitivity, and was generally well tolerated.
As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear.Double-blind randomized controlled trials comparing the efficacy of initial combination therapy of metformin and DPP-4 inhibitors with metformin monotherapy were included. The primary outcome was a result of comparisons between high-dose combination therapy and low-dose combination therapy in terms of efficacy and safety.A total of 11 studies were included. The results indicated that the high-dose combination therapy showed significant decreases in hemoglobin A1c (HbA1c) (-0.32%, P < 0.05), fasting plasma glucose (FPG) (-0.63 mmol/L, P < 0.05), and postprandial glucose (PPG) (-0.99 mmol/L, P < 0.05), but less increase in body weight (-0.54 kg, P < 0.05) when compared with low-dose combination therapy, corrected by metformin monotherapy. Moreover, the high-dose combination therapy exhibited significant decreases in HbA1c (-0.24%, P < 0.05), FPG (-0.54 mmol/L, P < 0.05), and PPG (-0.94 mmol/L, P < 0.05) in the Caucasian population than in the Asian population, corrected by metformin monotherapy.As an initial treatment, the high dose of metformin in combination with DPP-4 inhibitors not only provided better glycemic control but also had less effect on weight gain compared with the low-dose combination therapy through the correction of metformin monotherapy. Moreover, initial combination therapy in the Caucasian population showed better glycemic control and less increase in body weight compared with the Asian population.
Metabolic diseases such as obesity and diabetes have been the most serious social and health problems in the world. Current treatments mainly focus on the disease consequence rather than the cause of metabolic disorders, and it is difficult to curb the global trend of explosive growth of patients. Thus new and more effective prevention and treatment strategies are needed. Genetics and environment influence the process of obesity and diabetes. But the genomic analysis only accounts for 10% to 20% of the metabolic diseases, while environmental factors such as diet and other lifestyle habits play an important role in the onset of metabolic diseases. In recent years, an increasing number of studies have shown that human gut microbiota is closely related to the onset and development of metabolic diseases such as obesity and type 2 diabetes. The rapid progress in this emerging academic field will not only help elucidate the pathogenesis of metabolic disease, but will also provide direction for exploring new therapeutic targets and pathways.
Key words:
Obesity; Diabetes mellitus, type 2; Gut microbiota
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