A Randomized Controlled Clinical Trial of Lifestyle Intervention and Pioglitazone for Normalization of Glucose Status in Chinese with Prediabetes

Aims. Prediabetes has been proved as an important risk factor of both diabetes and cardiovascular disease (CVD). Previous studies have shown that both lifestyle intervention and pioglitazone may delay the development of diabetes in patients with prediabetes. However, no study has ever explored whether these interventions could revert prediabetes to normal glycemic status as the primary outcome. Interventions that may revert prediabetes back to normal glucose status would be of great clinical importance. Materials and Methods. We conducted a randomized, multicenter, 2 × 2 factorial designed study to examine whether intensive lifestyle intervention and/or pioglitazone could revert prediabetes to normal glucose tolerance. The participants were followed up for three years unless they reverted to normal glucose state or developed diabetes at the annual oral glucose tolerance test (OGTT). Reversion to normal glucose tolerance was confirmed on the basis of the results of OGTT. Results. In our study, 1945 eligible patients were ultimately randomized into four groups. In this three-year follow-up study, overall, 60.0%, 50.3%, 56.6% and 65.1% reverted back to normoglycemic state over 3 years of follow-up in the conventional lifestyle intervention plus placebo, intensive lifestyle intervention plus placebo, conventional lifestyle intervention plus pioglitazone, and intensive lifestyle intervention plus pioglitazone groups, respectively. Compared to the conventional lifestyle intervention plus placebo group, all the other three groups did not show any significant benefit in terms of reverting back to normoglycemic state. Conclusion. In our study, for patients with prediabetes, neither intensive lifestyle intervention nor pioglitazone had led to a higher reversion rate to normal glucose state. Trail registration.http://www.chictr.org.cn: ChiCTR-PRC-06000005.

The Depletion of Carbohydrate Metabolic Genes in the Gut Microbiome Contributes to the Transition From Central Obesity to Type 2 Diabetes

Obesity, especially central obesity, is a strong risk factor for developing type 2 diabetes (T2D). However, the mechanism underlying the progression from central obesity to T2D remains unknown. Therefore, we analyzed the gut microbial profiles of central obese individuals with or without T2D from a Chinese population. Here we reported both the microbial compositional and gene functional alterations during the progression from central obesity to T2D. Several opportunistic pathogens were enriched in obese T2D patients. We also characterized thousands of genes involved in sugar and amino acid metabolism whose abundance were significantly depleted in obese T2D group. Moreover, the abundance of those genes was negatively associated with plasma glycemia level and percentage of individuals with impaired plasma glucose status. Therefore, our study indicates that the abundance of those depleted genes can be used as a potential biomarker to identify central obese individuals with high risks of developing T2D.

Impact of prior cerebrovascular disease and glucose status on incident cerebrovascular disease in Japanese

Background Although both a history of cerebrovascular disease (CVD) and glucose abnormality are risk factors for CVD, few large studies have examined their association with subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose status, and their combinations on subsequent CVD using real-world data. Methods This is a retrospective cohort study including 363,627 men aged 18–72 years followed for ≥ 3 years between 2008 and 2016. Participants were classified as normoglycemia, borderline glycemia, or diabetes defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD (i.e. ischemic stroke, transient ischemic attack, and non-traumatic intracerebral hemorrhage) were identified according to claims using ICD-10 codes, medical procedures, and questionnaires. Results Participants’ mean age was 46.1 ± 9.3, and median follow up was 5.2 (4.2, 6.7) years. Cox regression analysis showed that prior CVD + conferred excess risk for CVD regardless of glucose status (normoglycemia: hazard ratio (HR), 8.77; 95% CI 6.96–11.05; borderline glycemia: HR, 7.40, 95% CI 5.97–9.17; diabetes: HR, 5.73, 95% CI 4.52–7.25). Compared with normoglycemia, borderline glycemia did not influence risk of CVD, whereas diabetes affected subsequent CVD in those with CVD- (HR, 1.50, 95% CI 1.34–1.68). In CVD-/diabetes, age, current smoking, systolic blood pressure, high-density lipoprotein cholesterol, and HbA1c were associated with risk of CVD, but only systolic blood pressure was related to CVD risk in CVD + /diabetes. Conclusions Prior CVD had a greater impact on the risk of CVD than glucose tolerance and glycemic control. In participants with diabetes and prior CVD, systolic blood pressure was a stronger risk factor than HbA1c. Individualized treatment strategies should consider glucose tolerance status and prior CVD.

Impact of Prior Cerebrovascular Disease and Glucose Status on Incident Cerebrovascular Disease in Japanese

Background: Although both a history of cerebrovascular disease (CVD) and glucose abnormality are risk factors for CVD, few large studies have examined their association with subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose status, and their combinations on subsequent CVD using real-world data. Methods: This is a retrospective cohort study including 363,627 men aged 18-72 years followed for ≥3 years between 2008 and 2016. Participants were classified as normoglycemia, borderline glycemia, or diabetes defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD (i.e. ischemic stroke, transient ischemic attack, and non-traumatic intracerebral hemorrhage) were identified according to claims using ICD-10 codes, medical procedures, and questionnaires. Results: The subjects’ mean age was 46.1 ± 9.3, and median follow up was 5.2 (4.2, 6.7) years. Cox regression analysis showed that prior CVD+ conferred excess risk for CVD regardless of glucose status (normoglycemia: hazard ratio (HR) , 8.77; 95% CI, 6.96-11.05; borderline glycemia: HR, 7.40, 95% CI, 5.97-9.17; diabetes: HR, 5.73, 95% CI, 4.52-7.25). Compared with the normoglycemia, borderline glycemia did not influence risk of CVD, whereas diabetes affected subsequent CVD in those with CVD- (HR, 1.50, 95% CI, 1.34-1.68). In CVD-/diabetes, age, current smoking, systolic blood pressure, HDL cholesterol, and HbA1c were associated with risk of CVD, but only systolic blood pressure was related to CVD risk in CVD+/diabetes.Conclusions: Prior CVD had a greater impact on risk of CVD than glucose tolerance and glycemic control. In diabetes with prior CVD, systolic blood pressure was a stronger risk factor than HbA1c. Individualized treatment strategy should consider glucose tolerance status and prior CVD.

Associations of Systolic Blood Pressure and Diastolic Blood Pressure With the Incidence of Coronary Artery Disease or Cerebrovascular Disease According to Glucose Status

<b>Aims: </b>To determine associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with new-onset coronary artery disease (CAD) or cerebrovascular disease (CVD) according to glucose status. <p><b>Research Design and Methods: </b>Examined was a nationwide claims database from 2008 – 2016<b> </b>on 593,196 individuals. Cox proportional hazards model identified risks of CAD and CVD events among 5 levels of SBP and DBP. </p> <p><b>Results:</b> During the study period 2,240 CAD and 3,207 CVD events occurred. Compared with SBP ≤119 mmHg, which was the lowest quintile of SBP, hazard ratios (HRs) (95% confidence interval) for CAD/CVD in the 4 higher quintiles (120-129, 130-139, 140-149, ≥150 mmHg) gradually increased from 2.10 (1.73 to 2.56)/ 1.46 (1.27 to 1.68) in quintile 2 to 3.21 (2.37 to 4.34)/4.76 (3.94 to 5.75) in quintile 5 for normoglycemia; from 1.39 (1.14 to 1.69)/1.70 (1.44 to 2.10) in quintile 2 to 2.52 (1.95 to 3.26)/4.12 (3.38 to 5.02) in quintile 5 for borderline glycemia; and from 1.50 (1.19 to 1.90)/1.72 (1.31 to 2.26) in quintile 2 to 2.52 (1.95 to 3.26)/3.54 (2.66 to 4.70) in quintile 5 for diabetes. A similar trend was observed for DBP across 4 quintiles (75-79, 80-84, 85-89, ≥90 mmHg) compared with ≤74 mmHg, which was the lowest quintile. </p> <p><b>Conclusions: </b>Results indicated that cardiovascular risks gradually increased with increases in SBP and DBP regardless of the presence of and degree of a glucose abnormality. Further interventional trials are required to apply findings from this cohort study to clinical practice. </p>

Associations of Systolic Blood Pressure and Diastolic Blood Pressure With the Incidence of Coronary Artery Disease or Cerebrovascular Disease According to Glucose Status

<b>Aims: </b>To determine associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with new-onset coronary artery disease (CAD) or cerebrovascular disease (CVD) according to glucose status. <p><b>Research Design and Methods: </b>Examined was a nationwide claims database from 2008 – 2016<b> </b>on 593,196 individuals. Cox proportional hazards model identified risks of CAD and CVD events among 5 levels of SBP and DBP. </p> <p><b>Results:</b> During the study period 2,240 CAD and 3,207 CVD events occurred. Compared with SBP ≤119 mmHg, which was the lowest quintile of SBP, hazard ratios (HRs) (95% confidence interval) for CAD/CVD in the 4 higher quintiles (120-129, 130-139, 140-149, ≥150 mmHg) gradually increased from 2.10 (1.73 to 2.56)/ 1.46 (1.27 to 1.68) in quintile 2 to 3.21 (2.37 to 4.34)/4.76 (3.94 to 5.75) in quintile 5 for normoglycemia; from 1.39 (1.14 to 1.69)/1.70 (1.44 to 2.10) in quintile 2 to 2.52 (1.95 to 3.26)/4.12 (3.38 to 5.02) in quintile 5 for borderline glycemia; and from 1.50 (1.19 to 1.90)/1.72 (1.31 to 2.26) in quintile 2 to 2.52 (1.95 to 3.26)/3.54 (2.66 to 4.70) in quintile 5 for diabetes. A similar trend was observed for DBP across 4 quintiles (75-79, 80-84, 85-89, ≥90 mmHg) compared with ≤74 mmHg, which was the lowest quintile. </p> <p><b>Conclusions: </b>Results indicated that cardiovascular risks gradually increased with increases in SBP and DBP regardless of the presence of and degree of a glucose abnormality. Further interventional trials are required to apply findings from this cohort study to clinical practice. </p>

Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant

Introduction Disorders of glucose metabolism are a serious acromegaly comorbidity and may be differently impacted by medical treatments of acromegaly. In this retrospective longitudinal multicenter study, we investigated the outcome of glucose metabolism and its predictors in patients treated with Pasireotide LAR (PAS-LAR) alone or in combination with Pegvisomant (PAS-LAR + Peg-V). Subjects and methods Acromegaly patients treated continously with PAS-LAR or PAS-LAR + Peg-V for at least 6 months. Results Forty patients (25 females, 15 males) were enrolled. At last visit, 27/40 patients (67.5%) reached biochemical control of acromegaly. Overall, glucose metabolism improved in 3 (all in PAS-LAR + Peg-V; 7.5%), worsened in 26 (65%) and remained unchanged in 11 patients (27.5%). Glucose metabolism worsened in 25 patients (73.5%) treated with PAS-LAR and in a single patient (16.7%) treated with PAS-LAR + Peg-V (p < 0.001). Among patients treated with Pas-LAR alone, GH at baseline was higher in those with worsening of glucose metabolism (p = 0.04) as compared to those with stable glucose status. A significantly higher reduction of HbA1c was observed in patients treated with PAS-LAR + Peg-V, as compared with those treated with PAS-LAR alone (p = 0.005). Conclusions Our data confirmed that glucose metabolism in patients treated with PAS-LAR is often worsened, and may be predicted by entity of baseline GH hypersecretion and by the dose of PAS-LAR. Moreover, our data, although limited by small numbers, may suggest that the combination treatment PAS-LAR + Peg-V can improve glucose homeostasis in selected patients.

Prognostic value of NT-proBNP in patients with chronic coronary syndrome and normal left ventricular systolic function according to glucose status: a prospective cohort study

Background The prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with coronary artery disease (CAD) with different glucose status has not been established. This study sought to evaluate the significance of NT-proBNP in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) and normal left-ventricular systolic function (LVSF) according to different glucose status, especially in those with abnormal glucose metabolism. Methods A total of 8062 patients with CCS and normal LVSF were consecutively enrolled in this prospective study. Baseline plasma NT-proBNP levels were measured. The follow-up data of all patients were collected. Kaplan-Meier and Cox regression analyses were used to assess the risk of MACEs according to NT-proBNP tertiles stratified by glucose status. Results Over an average follow-up of 59.13 ± 18.23 months, 569 patients (7.1 %) suffered from MACEs, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Kaplan-Meier analysis showed that high NT-proBNP levels had a significant association with MACEs in subjects with prediabetes mellitus (pre-DM) or DM, but not in patients with normoglycemia. Multivariate Cox regression analysis revealed that NT-proBNP remained an independent predictor of MACEs in patients with pre-DM [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.34–4.91] or DM (HR: 2.34, 95% CI: 1.32–4.16). Moreover, adding NT-proBNP to the original Cox model including traditional risk factors significantly increased the C-statistic by 0.035 in pre-DM and DM, respectively. Conclusions The present study indicated that NT-proBNP could well predict worse outcomes in dysglycemic patients with CCS and normal LVSF, suggesting that NT-proBNP may help with risk stratification in this population.