Change in glycated haemoglobin levels after initiating second‐line therapy in type 2 diabetes: a primary care database study

The aim of the present study was to compare the absolute reduction in glycated haemoglobin (HbA1c) levels at 6 months after initiating second‐line glucose‐lowering therapy in patients with type 2 diabetes treated with metformin monotherapy in general practices. A total of 7009 patients were identified (Disease Analyser Germany: January 2004 to December 2014). The patients' mean ± standard deviation (s.d.) age was 63 ± 11 years, 55.5% were male and their mean ± s.d. HbA1c level was 8.0 ± 1.6%. The initiated second‐line therapies included: dipeptidyl peptidase‐4 (DPP‐4) inhibitors (38.7%); sulphonylureas (36.3%); insulin (13.3%); glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs; 2.5%); thiazolidinediones (5%); and other agents (glinides, aldose‐reductase inhibitors; 4.1%). The mean absolute HbA1c change from baseline was ?0.9% (DPP‐4 inhibitors, ?0.9%; sulphonylureas, ?0.9%; insulin, ?1.1%; GLP‐1RAs, ?0.7%; thiazolidinediones, ?0.9%; and other, ?0.7%; all p < 0.001). Overall, 58% of patients reached the HbA1c target of <7% (DPP‐4 inhibitors, 61.7%; sulphonylureas, 56.7%; insulin, 45.6%; GLP‐1RAs, 62.2%; thiazolidinediones, 69.7%; and other, 57.5%). Compared with sulphonlyureas, DPP‐4 inhibitors, GLP‐1RAs and thiazolidinediones were associated with an increased odds of reaching HbA1c <7% [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.09–1.40; OR 1.43, 95% CI 1.01–2.04; and OR 1.70, 95% CI 1.30–2.23, respectively], whereas insulin was related to a lower odds (0.66, 95% CI 0.55–0.78). In conclusion, in patients with type 2 diabetes very similar reductions in HbA1c after 6 months of second‐line therapy were achieved regardless of the type of therapy.     

Long-term exendin-4 treatment delays natural deterioration of glycaemic control in diabetic Goto–Kakizaki rats

Aim: The glucagon-like peptide-1 (GLP-1) receptor agonist, exendin-4, has previously been shown to delay the onset of diabetes when administered to Goto–Kakizaki (GK) rats in the prediabetic period. The present study aimed to evaluate whether long-term administration of exendin-4 to GK rats in the diabetic period would improve their diabetes and how glycaemic control was affected following drug wash-out.
Methods: Glycaemic control was assessed in diabetic GK rats during 12 weeks of exendin-4 or vehicle treatment. Moreover, some animals were followed for an additional 9 weeks without treatment.
Results: Glycaemic control was seen to deteriorate in vehicle-treated animals, as assessed by increased glycated haemoglobin A1c (HbA1c), whereas HbA1c improved in exendin-4-treated animals. Following an additional 9 weeks without treatment, glycaemic control in exendin-4-treated animals remained below baseline value and thus remained significantly lower than that of vehicle-treated animals. Following exendin-4 administration, oral glucose tolerance tests revealed greatly reduced glucose and insulin excursions compared with vehicle-treated animals, whereas following overnight drug wash-out, only little difference was seen, suggesting that the improvement in glycaemic control may have been obtained primarily by increased postprandial control. No significant differences were observed in pancreatic islet morphology or islet hormone content.
Conclusions: Exendin-4 treatment improved glycaemic control in diabetic GK rats, independent of changes in β-cell mass. Additionally, progression of the disease seemed to be delayed because the improvement in HbA1c was still apparent 9 weeks after cessation of treatment.     

Glycaemic control and sepsis risk in adults with type 1 diabetes

Aims

To study the association between glycated haemoglobin (HbA1c) and sepsis in adults with type 1 diabetes, and to explore the relationship between HbA1c and mortality among individuals who developed sepsis.

Materials and Methods

We included 33 549 adult individuals with type 1 diabetes recorded in the Swedish National Diabetes Register between January 2005 and December 2015. We used multivariable Cox regression and restricted cubic spline analyses to study the relationship between HbA1c values and sepsis occurrence and association between HbA1c and mortality among those with sepsis.

Results

In total, 713 (2.1%) individuals developed sepsis during the study period. Compared with the HbA1c reference interval of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was: 2.50 [95% confidence interval (CI) 1.18-5.29] for HbA1c <43 mmol/mol; 1.88 (95% CI 0.96-3.67) for HbA1c 43-47 mmol/mol; 1.78 (95% CI 1.09-2.89) for HbA1c 53-62 mmol/mol; 1.86 (95% CI 1.14-3.03) for HbA1c 63-72 mmol/mol; 3.15 (95% CI 1.91-5.19) for HbA1c 73-82 mmol/mol; and 4.26 (95% CI 2.53-7.16) for HbA1c >82 mmol/mol. On multivariable restricted cubic spline analysis, we found a J-shaped association between HbA1c and sepsis risk, with the lowest risk observed at HbA1c of approximately 53 mmol/mol. We found no association between HbA1c and mortality among those individuals who developed sepsis.

Conclusions

In our nationwide observational study of adult individuals with type 1 diabetes we found a J-shaped relationship between HbA1c and risk of sepsis, with the lowest risk at HbA1c levels about 53 mmol/mol (7.0%). HbA1c was not associated with mortality in individuals affected by sepsis.     

Thermolabile methylenetetrahydrofolate reductase enzyme genotype is frequent in type 2 diabetic patients with normal fasting homocysteine levels

OBJECTIVE: To investigate the plasma homocysteine concentrations with regard to nutritional, metabolic and genetic factors and to find out the frequency and impact of thermolabile methylenetetrahydrofolate reductase (T-MTHFR) polymorphism in patients with type 2 diabetes mellitus. DESIGN: A cross-sectional study. SUBJECTS: A total of 94 subjects with type 2 diabetes mellitus and 91 healthy age- and sex-matched nonsmoking volunteers were recruited. MAIN OUTCOME MEASURES: Age, sex, duration and complications of diabetes mellitus, metabolic variables, fasting plasma homocysteine levels, and presence of T-MTHFR polymorphism were evaluated for all participants. Presence of T-MTHFR polymorphism was analysed to define any possible role in diabetes progress, complications and metabolic milieu. RESULTS: Fasting homocysteine levels were similar in diabetic patients and controls. Prevalence of homozygous polymorphism of thermolabile MTHFR gene (TT) was encountered more frequently in patients with diabetes mellitus than the healthy controls (P = 0.004). Subgrouping of the patients with respect to MTHFR genotype revealed similar metabolic variables and frequency of chronic complications of diabetes mellitus in groups. Patients with TT genotype revealed longer diabetes duration when compared with the patients having heterozygous mutation of thermolabile MTHFR or normal homozygous MTHFR genotypes (P = 0.046). CONCLUSIONS: Type 2 diabetic patients have similar fasting plasma homocysteine levels with that of age- and sex-matched healthy people. There is no correlation between diabetic complications and this amino acid metabolite. On the contrary, thermolabile variant of MTHFR genotype is found to be more frequent in diabetic patients especially in those who have experienced a longer duration of disease.     

Effect of a pocket-size tablet-dispensing device on glycaemic control in Type 2 diabetic patients.

AIM: To evaluate whether a pocket-size tablet-dispensing device would improve adherence to therapy as judged by reduction of HbA(1c) levels in a large population of Type 2 diabetic patients. METHODS: The study design was prospective, randomized, open label with two parallel groups. Patients (2296) were recruited from general practitioners and internists and randomized to either receive a tablet dispenser (TD) or no intervention (control group, CO). Patients' characteristics and current oral therapy (including dosage) were recorded at baseline. HbA(1c) was compared between groups at baseline and after 6 months' intervention. RESULTS: Data were available in 2081 patients. Baseline characterisitcs, including age, body mass index (BMI), blood pressure and gender distribution were comparable between the two groups, as was HbA(1c)[7.9 (7.9-8.0), TD vs. 8.0 (7.9-8.0)%, CO, means (95% CI)]. After 6 months, HbA(1c) improved in both groups, but improvement was significantly greater in TD than in controls [-0.74 (0.67-0.80) vs. -0.53 (0.47-0.59)%, P < 0.0001]. Possession of a dispenser remained an independent predictor of improved control in a multiple regression model. In the subgroup analysis, the effect was significantly more pronounced (i) in patients receiving more medications and (ii) more diabetes medications per day (iii) in younger patients. CONCLUSION: In this large study population in a 'realistic' setting, a simple tablet-dispensing device led to a significant and clinically relevant improvement in HbA(1c) levels. Because patients with a more complex therapy regimen benefited more, we suggest that TD might have improved adherence to therapy.     

江苏省2型糖尿病患者血糖控制及治疗用药情况调查

目的了解江苏省2型糖尿病（T2DM）患者的血糖控制情况,分析治疗方法与血糖控制的关系。方法采用横断面研究方法,以调查问卷形式收集患者年龄、病程、降糖药物的使用情况等,留取血标本检测HbA1c。根据HbA1c水平将患者分为达标组（HbA1c〈6．5％）和未达标组（HbA1c≥6．5％）;根据降糖治疗情况分为胰岛素（Ins）组、胰岛素联用口服降糖药（Ins＋OA）组、口服降糖药（OA）组、生活方式干预（LS）组。结果入选T2DM患者2966例,年龄（56．4±11．2）岁,糖尿病平均病程（6．3±5．7）年,HbA1c值（7．2±1．6）％,HbA1c≥6．5％的患者占59．8％。（1）平均病程Ins组[（7．6±6．5）年]与Ins＋OA组[（8．2±6．2）年]均高于OA组C（5．3±5．0）年]（P〈0．01）。HbA1c均值及未达标比例Ins组[（7．4±1．6）％,未达标比例65．9％]与Ins＋OA组[（7．5±1．5）％,未达标比例77．9％]均高于OA组[（7．0±1．6）％,未达标比例52．4％]（P〈0．01）。（2）HbA1c达标组与未达标组病程分别为（4．8±4．9）年和（7．3±6．1）年（P〈0．01）,两组中胰岛素联合口服降糖药治疗者分别占11．5％和27．2％（P〈0．01）,单用胰岛素治疗者分别占17．0％和22．1％（P〈0．01）。结论江苏省T2DM患者血糖控制现状比3年前全国调查情况有所改善,但仍有相当比例的患者HbA1c水平没有达到IDF及《中国2型糖尿病防治指南》推荐标准。接受胰岛素治疗的患者HbA1c均值及不达标比例明显高于其他治疗组,表明由于病程延长及口服降糖药用药失效导致病情恶化后,再选择胰岛素治疗,血糖控制情况并不理想。     

Smoking cessation and glycaemic control in type 2 diabetic patients

Aim:  To elucidate the relationship between glycaemic control, blood pressure and body-weight change after smoking cessation in type 2 diabetic patients.
Methods:  We examined HbA_1c, blood pressure and body weight in 15 type 2 diabetic patients before, 6 and 12 months after quitting smoking. Sixteen type 2 diabetic patients who did not quit smoking served as control.
Results:  Body weight slightly increased after quitting smoking. Although HbA_1c levels showed no change in the control group, those in patients who quit smoking significantly increased (6.8 ± 0.3% before quitting smoking; 7.4 ± 0.3% 6 months after quitting smoking, p < 0.05; 7.8 ± 0.4% 12 months after quitting smoking, p < 0.001). Fasting blood glucose also increased in patients who quit smoking. The increase in body weight after quitting smoking did not correlate with the deterioration of glycaemic control. Diastolic blood pressure showed no change in control, whereas that in patients who quit smoking increased at month 12 (69 ± 3 vs. 76 ± 3 mmHg, p < 0.01). The increase in HbA_1c at month 12 after quitting smoking correlated with body mass index before quitting smoking ( r  = 0.72, p < 0.005) and serum triglyceride before quitting smoking ( r  = 0.68, p < 0.01).
Conclusions:  Glycaemic control and diastolic blood pressure deteriorated in type 2 diabetic patients after quitting smoking. Type 2 diabetic patients who want to stop smoking need a caution to prevent deterioration of glycaemic control and blood pressure after quitting smoking.     

2型糖尿病患者不同HbA1c水平和骨代谢指标的关系

目的 观察2型糖尿病患者不同HbA1c水平对骨代谢指标骨γ-羧谷氨酸包含蛋白(骨钙素)、Ⅰ型胶原交联羧基端肽(CTX-Ⅰ)、碱性磷酸酶(ALP)的影响.方法 选取2013年10月—2014年1月在哈尔滨医科大学附属第二医院内分泌科住院的120例男性2型糖尿病患者和来自体检中心的40名健康男性作为研究对象.将120例2型糖尿病患者根据HbA1c水平分为为HbA1c≤7％组、HbA1c 7％～ 9％组、HbA1c≥9％组,将40名健康男性作为对照组.采集其年龄、体重指数、病程及血钙、血磷、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶等临床指标,检测血清HbA1c、骨钙素、CTX-Ⅰ、ALP等指标.对4组间HbA1c水平与骨钙素、CTX-Ⅰ、ALP进行相关性和回归分析.结果 与对照组相比,HbA1c≤7％组、HbA1c 7％～9％组及HbA1c≥9％组血清骨钙素水平显著降低(F=7.211,P<0.05),血清ALP、CTX-Ⅰ水平显著升高(F=4.382、809.475,P<0.05);与HbA1c≤7％组相比,HbA1c7％～ 9％组和HbA1c≥9％组血清ALP水平显著降低(P<0.05),血清CTX-Ⅰ水平显著升高(P<0.05);与HbA1c7％～9％组相比,HbA1c≥9％组血清骨钙素水平显著降低(P<0.05),血清CTX-Ⅰ水平显著升高(P<0.05).Spearman相关分析发现,骨钙素与空腹血糖(r=-0.249,P=0.002)、糖化白蛋白(GA,r=-0.321,P=0.000)、HbA1c(r=-0.288,P=0.000)水平呈负相关,ALP、CTX-Ⅰ与空腹血糖(r=0.218、0.321)、GA(r =0.302、0.291)、HbA1c(r =0.321、0.238)水平呈正相关(P均<0.01).进一步经线性回归分析发现,骨钙素水平与GA(β=-0.086,P=0.008)、HbA1c(β=-0.502,P=0.001)呈负相关,CTX-Ⅰ水平与空腹血糖(β=0.042,P =0.003)、GA (β=0.007,P=0.015)、HbA1c(β=0.037,P=0.009)呈正相关.结论 2型糖尿病患者存在骨代谢指标异常,且HbA1 c与骨钙素、CTX-Ⅰ水平相关.     

Effect of metformin plus roziglitazone compared with metformin alone on glycaemic control in well-controlled Type 2 diabetes.

Aims To investigate the effect of metformin plus roziglitazione (RSGMET) compared with metformin alone (MET) on glycaemic control in well‐controlled Type 2 diabetes. Methods Subjects (drug naïve or those on glucose‐lowering monotherapy) were randomized (n = 526), following a 4‐week placebo run‐in period, to RSGMET [4 mg rosiglitazone (RSG)/500 mg MET] or MET 500 mg. From weeks 2–18, medication was escalated every 4 weeks (based on gastrointestinal tolerability), then remained at RSGMET 8 mg/2 g or MET 3 g for 14 weeks. Results RSGMET reduced HbA_1c from 7.2 ± 0.6 to 6.7 ± 0.8% at week 32, compared with a reduction from 7.2 ± 0.6 to 6.8 ± 0.9% with MET (treatment difference ?0.13%; P = 0.0357). More subjects achieved an HbA_1c value of ≤ 6.5% at week 32 with RSGMET (51.6 vs. 43.7%), but the treatment difference was not significant (odds ratio 1.37, P = 0.0949). RSGMET produced larger reductions from baseline in mean fasting plasma glucose (adjusted difference ?0.62 mmol/l, P < 0.0001), with the odds ratio of achieving a target of < 7.0 mmol/l being 2.33 (P < 0.0001). Statistically significant differences in favour of RSGMET relative to MET were seen for homeostatic model assessment (HOMA)‐derived estimates of insulin sensitivity and pancreatic B‐cell function, C‐reactive protein (CRP), and systolic blood pressure. Overall rates of gastrointestinal adverse events (relevant to the known profile of MET) were comparable, but with a lower incidence of diarrhoea (8 vs. 18%) with RSGMET. Hypoglycaemia was reported in ≤ 7% subjects per group. Conclusions RSGMET provided similar short‐term glycaemic control to MET with greater improvements in estimates of insulin sensitivity, B‐cell function and CRP, with less diarrhoea and low risk of biochemical hypoglycaemia, suggesting that early use of combination therapy may be appropriate.     

Acarbose and metabolic control in patients with type 2 diabetes with newly initiated insulin therapy

AIM: This study was designed to investigate the effect of acarbose in patients with type 2 diabetes with newly initiated insulin treatment who had previously been insufficiently controlled with oral antihyperglycaemic agents [haemoglobin A(1c) (HbA(1c)) >/= 8%]. METHODS: In this 20-week double-blind, placebo-controlled study, 163 patients were randomized to receive acarbose up to 100 mg three times a day or matching placebo. Both the groups were newly initiated with insulin, which was adjusted according to blood glucose values. Primary efficacy parameter was the change in HbA(1c) from baseline; changes in daily insulin doses were also assessed. RESULTS: Mean HbA(1c) was significantly reduced by acarbose compared with placebo (2.31 vs. 1.81%, p = 0.033). Insulin doses were comparable at the end of the study. There was no difference in blood glucose and triglyceride levels between the treatment groups. Postprandial serum insulin levels increased in both treatment arms owing to insulin administration but less so under acarbose. In contrast to the placebo group, an increase in body mass index was prevented for acarbose-treated patients. CONCLUSION: As adjunct administration to newly initiated insulin therapy, acarbose enhances the optimization of blood glucose control in patients with type 2 diabetes.     

Adherence to a Mediterranean diet and glycaemic control in Type 2 diabetes mellitus

Aims Mediterranean‐type diets reduce the risk of Type 2 diabetes. Whether a Mediterranean‐type diet improves glycaemic control in diabetes remains unknown. Methods We conducted a cross‐sectional analysis in 901 outpatients with Type 2 diabetes attending diabetes clinics located in Campania County, South Italy. We explored the relation between glycated haemoglobin (HbA_1c), measured centrally, self‐measured pre‐ and postprandial glucose levels and consumption of a Mediterranean‐type diet. Adherence to a Mediterranean‐type diet was assessed by a 9‐point scale that incorporated the salient characteristics of this diet (range of scores, 0–9, with higher scores indicating greater adherence). The study was conducted from 2001 to 2007. Results Diabetic patients with the highest scores (6–9) had lower body mass index and waist circumferences, a lower prevalence of the metabolic syndrome and lower HbA_1c and post‐meal glucose levels than diabetic patients with the lowest scores (0–3). In multivariate analysis, mean HbA_1c and 2‐h post‐meal glucose concentrations were significantly lower in diabetic patients with high adherence to a Mediterranean‐type diet than those with low adherence [difference: HbA_1c 0.9%, 95% confidence intervals (CI) 0.5–1.2%, P < 0.001; 2‐h glucose 2.2 mmol/l, 95% CI 0.8–2.9 mmol/l, P < 0.001]. Conclusions In Type 2 diabetes, greater adherence to a Mediterranean‐type diet is associated with lower HbA_1c and postprandial glucose levels.     

Prevalence and correlation of glycemic control achievement in patients with type 2 diabetes in Iraq: A retrospective analysis of a tertiary care database over a 9-year period

BackgroundThis study was designed to assess the achievement of a glycated hemoglobin (HbA1c) target in Iraqi type 2 diabetes mellitus (T2DM) patients via retrospective analysis of a tertiary care database over a 9-year period.MethodsA total of 12,869 patients with T2DM with mean (SEM) age: 51.4(0.1) years, and 54.4% were females registered into Faiha Specialized Diabetes, Endocrine and Metabolism Center(FDEMC) database between August 2008 and July 2017 were included in this retrospective study. Data were recorded for each patient during routine follow-up visits performed at the center every 3–12 months.ResultsPatients were under oral antidiabetic drugs (OAD; 45.8%) or insulin+ OAD (54.2%) therapy. Hypertension was evident in 42.0% of patients, while dyslipidemia was noted in 70.5%. Glycemic control (HbA1c <7%) was achieved by 13.8% of patients. Multivariate analysis revealed <55 years of age, female gender, >3 years duration of diabetes, HbA1c >10% at the first visit, presence of dyslipidemia, and insulin treatment as significant determinants of an increased risk of poor glycemic control. BMI <25 kg/m² and presence of hypertension were associated with a decreased risk of poor glycemic control.ConclusionUsing data from the largest cohort of T2DM patients from Iraq to date, this tertiary care database analysis over a 9-year period indicated poor glycemic control. Younger patient age, female gender, longer disease duration, initially high HbA1c levels, dyslipidemia, insulin treatment, overweight and obesity, and lack of hypertension were associated with an increased risk of poor glycemic control in Iraqi T2DM patients.     

Effect of nutrition on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully automated closed-loop insulin therapy

Fully automated closed-loop insulin delivery may offer a novel way to manage diabetes in hospital. However, postprandial glycaemic control remains challenging. We aimed to assess the effect of nutritional intake on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully closed-loop insulin therapy. The effects of different meal types and macronutrient composition on sensor glucose time-in-target (TIT, 3.9-10.0 mmol/L) and mean sensor glucose were assessed with hierarchical linear models using a Bayesian estimation approach. TIT was lower and the mean sensor glucose slightly higher, after breakfast compared with lunch and dinner, whereas the insulin dose was higher. Across meals, when carbohydrates were replaced by fat, or to a lesser extent by protein, postprandial glucose control improved. For breakfast, a 3.9% improvement in TIT was observed when 10% of the energy from carbohydrates was replaced by fat. Improvements were slightly lower during lunch and dinner (3.2% and 3.4%) or when carbohydrates were replaced by protein (2.2 and 2.7%, respectively). We suggest that reducing carbohydrate at the expense of fat or protein, could further improve glucose control during fully closed-loop insulin therapy in hospital.     

Ethnic differences in glycaemic control in adult Type 2 diabetic patients in primary care: a 3-year follow-up study.

OBJECTIVE: To evaluate ethnic differences and characteristics related to glycaemic control in patients with Type 2 diabetes in primary care. RESEARCH DESIGN AND METHODS: Prospective cohort study; 500 adult patients with Type 2 diabetes, who were not on insulin therapy, were followed up annually for 3 years. HbA(1c) at baseline and 3-year changes and subsequent insulin therapy were related to baseline characteristics. RESULTS: Malay patients had significantly higher HbA(1c) (mean 8.7% +/- sd 1.66) compared with Chinese (8.2 +/- sd 1.67) and Indian (8.2 +/- sd 1.55) (P = 0.032) at baseline, and consistently for all years of HbA(1c) assessment (P = 0.017). At baseline, Malay patients were significantly more obese than Chinese or Indians (P < 0.001); fewer of them received structured shared-care intervention (P = 0.001), but they had a significantly higher glucose control educational score (P < 0.05). Multivariable analyses showed that HbA(1c) at baseline was significantly related to age (P = 0.001), BMI (P = 0.031) and ethnicity (P = 0.002). HbA(1c) declined significantly over 3 years in the whole population and in all ethnic groups. Significantly greater HbA(1c) declines were associated with higher baseline HbA(1c), structured shared-care intervention and non-insulin therapy. Correcting for differences on these factors, the decline in HbA(1c) in Malays was significantly less than in the Chinese. Insulin therapy was associated with higher baseline HbA(1c) and higher BMI. CONCLUSIONS: Malay ethnicity was associated with persistently poor glycaemic control. Sociocultural and behavioural factors should be addressed in improving care for patients with poorly controlled diabetes.