Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes

AimUrinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions.MethodsWe studied hypertensive patients with early prediabetes (HbA1c < 5.7% and fasting glucose > 110, n = 18), those with prediabetes (HbA1c 5.7–6.4, n = 98), and those with diabetes (HbA1c > 6.5 or on diabetes medications, n = 92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e’). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e’ ≥ 15, or E/e’ = 9–14 accompanied by left atrial volume/BSA ≥ 32 ml/mm². Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c.ResultsUrinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes.ConclusionsIn hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP.     

Evaluation of unmet medical need among Japanese patients with type 2 diabetes mellitus and efficacy of Lixisenatide treatment among Asian type 2 diabetes mellitus patients

AimsThis study determined the unmet medical need of basal insulin therapy among type 2 diabetes patients who participated in the ALOHA study. Also a meta-analysis of the GetGoal-Duo1, -L, and -L-Asia trials was conducted to examine the impact of lixisenatide add-on treatment to basal insulin therapy ± OADs specifically among Asian type 2 diabetes patients.MethodsThe proportions of Japanese patients with an unmet need of diabetes management, defined as not achieving an HbA1c < 7% despite having a fasting plasma glucose (FPG) < 130 mg/dL, and without an unmet need, defined as having an endpoint HbA1c < 7%, regardless of FPG level, were determined for the ALOHA study population, which was conducted as a post-marketing survey for insulin glargine in Japan. For the meta-analysis, all Asian modified intent-to-treat patients with baseline and endpoint HbA1c measurements reported from the 3 GetGoal trials were included.ResultsAmong 1013 Japanese type 2 diabetes patients in the ALOHA study, 36% had an unmet need. In the GetGoal-Duo1, -L, and L-Asia trials, 237 Asian patients were treated with lixisenatide add-on treatment to basal insulin and 226 received placebo. Lixisenatide add-on treatment vs. placebo was associated with the following significant mean changes in efficacy outcomes at week 24: HbA1c: −0.6%, p = 0.005; FPG: −13.3 mg/dL, p = 0.004; PPG: −101.4 mg/dL, p < 0.001; weight: −0.5 kg, p = 0.018; basal insulin dose: −1.6 U, p < 0.001.ConclusionsLixisenatide add-on treatment may provide a viable option to address the unmet need of basal insulin therapy among Asian type 2 diabetes patients.     

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

AimsThe clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.MethodsWe recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3–6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7–6.4%, 39–46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.ResultsEighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥165 mg/dL and a 30-min C-peptide <5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98–26.16) of developing diabetes than other prediabetic subjects.ConclusionsIn Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.     

Prevalence of impaired glucose tolerance in ischemic Egyptian patients

Background and aimPrediabetes (impaired glucose tolerance or impaired fasting glucose) is usually associated with a higher health risk profile for cardiovascular diseases. To our knowledge, no data about its prevalence in Egyptian patients are available. We aimed to determine the prevalence of prediabetes among Egyptian patients who were known to be neither diabetic nor prediabetic & referred to undergo coronary angiography.Methods and resultsThe study included 1000 consecutive Egyptians in the Cairo governorate with no previous diagnosis of diabetes nor prediabetes, who underwent coronary angiography for suspected coronary artery disease. They were screened for having prediabetes with either impaired fasting glucose through checking their fasting blood sugar or impaired glucose tolerance through checking their 2 h postprandial blood sugar.Twenty-three percent of patients had prediabetes; either isolated impaired fasting glucose, isolated impaired glucose tolerance or both combined together. The mean age of all patients was 52.35 ± 7.02 years. 26.33% of female patients were prediabetic while 21.43% of male patients were prediabetic. Hypertensive prediabetic patients numbered 110 and most of them were females. Body Mass Index among prediabetic patients was higher than that among patients with normal glucose tolerance and in females more than males. Prediabetes was more prevalent among patients with acute coronary syndrome than among patients with chronic ischemic heart disease.ConclusionPrediabetes is prevalent among ischemic Egyptian patients at a considerable ratio and should be screened for.     

Status of serum magnesium in type 2 diabetes mellitus with particular reference to serum triacylglycerol levels

Magnesium (Mg) is the fourth most abundant cation in the body and the second most common intracellular cation. The association between hypomagnesemia and insulin resistance (IR) in diabetes mellitus has been documented earlier. However, we wanted to study whether the extracellular status of magnesium (Mg) could be a biochemical mediator between hypertriacylglycerolemia and diabetes mellitus.AimsTo find out the probable association among HbA1c, triacylglycerol (TG) and magnesium levels – a predictor of vascular complications in T₂DM.Materials and methodsThirty patients who had attended the diabetic clinics during the period of this study were included. All the samples were analysed for glucose, TG, Mg, and HbA1c. For statistical analysis, SPSS 17 package was used.ResultsSerum TG (236.67*, 195.06) and HbA1C (9.97*, 8.57) levels were independently compared between the two groups and were significantly high in group A subjects (Mg < 1.2 mg/dl) as compared to group B subjects (Mg > 1.2 mg/dl) (*p-value < 0.05), respectively.Discussion and conclusionHypertriacylglycerolemia was pronounced in type 2 diabetes mellitus patients with accompanying hypomagnesemia. This compared well with that of the glycemic control. Low Mg levels, high TG levels in association with enhanced HbA1c levels could thus serve as a reliable biochemical indicator of insulin status and action without resorting to the usage of criteria for insulin sensitivity and resistance.     

Screening for impaired fasting glucose and diabetes using available health plan data

AimsTo develop and validate prediction equations to identify individuals at high risk for type 2 diabetes using existing health plan data.MethodsHealth plan data from 2005 to 2009 from 18,527 members of a Midwestern HMO without diabetes, 6% of whom had fasting plasma glucose (FPG) ≥ 110 mg/dL, and health plan data from 2005 to 2006 from 368,025 members of a West Coast-integrated delivery system without diabetes, 13% of whom had FPG ≥ 110 mg/dL were analyzed. Within each health plan, we used multiple logistic regression to develop equations to predict FPG ≥ 110 mg/dL for half of the population and validated the equations using the other half. We then externally validated the equations in the other health plan.ResultsAreas under the curve for the most parsimonious equations were 0.665 to 0.729 when validated internally. Positive predictive values were 14% to 32% when validated internally and 14% to 29% when validated externally.ConclusionMultivariate logistic regression equations can be applied to existing health plan data to efficiently identify persons at higher risk for dysglycemia who might benefit from definitive diagnostic testing and interventions to prevent or treat diabetes.     

Follow-up of patients with hyperglycemia in the emergency department without a history of diabetes mellitus

ObjectivesThe aim of this study is to determine the prevalence of hyperglycemia in emergency department patients without a history of diabetes mellitus, and to investigate whether these patients were referred to a general practitioner or to the outpatient clinic for follow-up with further diagnostic testing and treatment.MethodsWe conducted a retrospective cohort pilot study of adult patients who were seen at the emergency department of an urban academic hospital in the Netherlands between the 1st of January and the 29th of February 2008, who had an initial (unknown fasting or non-fasting) plasma glucose level ≥ 7.8 mmol/L (140 mg/dL). The medical records of these patients were retrieved to evaluate whether these patients were referred for follow-up.ResultsDuring the data collecting period 5317 patients presented at the ED, 343 of these patients were identified with a plasma glucose ≥ 7.8 mmol/L. Using exclusion criteria, eventually 154 patients were included in this study. The prevalence of incidentally found hyperglycemia in emergency department patients without a history of diabetes mellitus in this period was 2.9%.For 98.7% of the hyperglycemic patients no follow-up was arranged by the treating physician. None of the patients was treated with a hypoglycemic agent in the emergency department.ConclusionA substantial percentage (2.9%) of our study population had hyperglycemia and thus was at risk for undiagnosed diabetes mellitus and prediabetes. To date, recognition and follow-up of hyperglycemia in emergency department patients is poor. We presume that major health benefits may be achieved when the follow-up of hyperglycemia is performed more frequently.     

Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

Background and aimsWe aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia.Methods and resultsNinety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39–46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39 mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT.ConclusionsSubjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases.     

Glycaemic control for painful diabetic peripheral neuropathy is more than fasting plasma glucose and glycated haemoglobin

BackgroundThe relationship between postprandial hyperglycaemia and diabetic peripheral neuropathy (DPN), whether painful or painless, has yet to be determined. Thus, the aim of this study was to investigate the relationship in patients with type 2 diabetes (T2D).MethodsThis cross-sectional study was conducted in adults with T2D between January and October 2013. Blood samples were collected after overnight fasting every 3 months prior to enrolment. For this study, increased postprandial glycaemic exposure was defined as high glycated haemoglobin (HbA_1c) and near-normal mean fasting plasma glucose (FPG) levels. Both painless and painful DPN were evaluated using two validated tools, the Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique 4 (DN4) questionnaire.ResultsThis study included 1040 participants with mean FPG levels < 140 mg/dL, 535 of which were < 126 mg/dL. Of these patients, 200/1040 (19.2%) and 105/535 (19.6%) had DPN. Multivariate analysis demonstrated that higher HbA_1c levels (≥ 7%) did not increase risk of painless DPN, but did significantly increase risk of painful DPN in T2D patients with FPG < 140 mg/dL and < 126 mg/dL, with corresponding odds ratios of 2.49 and 3.77 (95% confidence intervals: 1.09–5.71 and 1.20–11.79), respectively, after adjusting for demographic factors, diabetes-related variables and comorbidities.ConclusionThis study is the first to reveal that increased postprandial glycaemic exposure, as assessed by high HbA1c and near-normal FPG levels, is associated with an increased risk of painful DPN in adults with T2D.     

Influence of iron metabolism indices on HbA1c in non-diabetic pregnant women with and without iron-deficiency anemia: Effect of Iron supplementation

AimsCondition that influence erythrocyte turnover also affect HbA1c. Although many forms of anemia are associated with lowering of HbA1c, iron-deficiency anemia (IDA) tends to increase HbA1c. In this study, we examined the relationship between HbA1c and erythrocyte indices in non-diabetic pregnancy and assessed the effect of iron supplementation on HbA1c.Materials and Methods150 women were studied (30 non-diabetic), non-pregnant, non-anemic women in child bearing women with varying parity as controls (Gp 1); 30 non-diabetic, non-anemic pregnant women in first trimester of pregnancy (Gp 2a); 30 non-diabetic, non-anemic pregnant women in second trimester of pregnancy (Gp 2b); 30 non-diabetic, non-anemic pregnant women in third trimester of pregnancy (Gp 2c) and 30 non-diabetic pregnant women with IDA (Gp 2d). HbA1c, OGTT, erythrocyte indices and iron metabolic indices were determined in Gp 2d subjects not supplemented with iron and repeated these indices after 3 months of iron-supplementation.ResultsThe mean fasting and postprandial blood glucose levels (79.9 ± 8.0 mg/dl, 108.1 ± 14.1 mg/dl) in Gp 1 were found to be significantly lower in first trimester among Gp 2a (74.4 ± 5.3 mg/dl and 97.2 ± 11.1 mg/dl), in second trimester among Gp 2b (76.2 ± 5.2 mg/dl and 103.4 ± 7.9 mg/dl) followed by increase in IIIrd trimester among Gp 2c (82.3 ± 5.7 mg/dl and 112.5 ± 8.5 mg/dl) subjects. A significant difference in HbA1c was also observed among the groups (HbA1c 4.7 ± 0.3% in Gp 1; 4.6 ± 0.4% in Gp 2a; 4.5 ± 0.3 in Gp 2b; 4.7 ± 0.3 in Gp 2c). Among Gp 2d subjects, HbA1c was 5.2 ± 0.3% and the level decreased after iron supplementation to 5.1 ± 0.3%. Significant correlation between erythrocyte indices, iron metabolic indices and HbA1c was also observed.ConclusionWe conclude that consideration should be given for performing glucose testing in patients with IDA to ascertain the reliability of HbA1c in the diagnosis of diabetes. HbA1c concentrations in diabetic patients with IDA should be interpreted with caution.     

Blood glucose and cholesterol levels in adult population of Bangladesh: Results from STEPS 2006 survey

BackgroundA nationally representative survey was carried out to determine the distribution of blood glucose and cholesterol in adult population of Bangladesh in the absence of existing data.MethodsThe study adopted a multistage and geographically clustered sampling technique of households. A total of 2610 individuals (1444 men and 1166 women) aged 25–64 years were selected from rural and urban areas. Capillary blood glucose and total cholesterol levels were measured using an overnight fasting state.ResultsThe mean age of the participants was 41 years [standard deviation (SD), 11 years]. Half of them (49%) were from urban areas. Half of them (51%) had primary or higher education. Mean glucose was 74 mg/dL (SD 23 mg/dL). Men had higher mean glucose levels (79 mg/dL) than women (67 mg/dL). Age-standardized prevalence of diabetes (blood glucose level ≥126 mg/dL and/or use of anti-diabetic medication) was 5.5%. In men, it was almost two-and-half times (7.6%) compared with women (2.8%). It was also double in urban areas (7.8%) compared with rural areas (3.4%). Mean cholesterol level among all participants was 167 mg/dL (SD 26 mg/dL). Men and women had almost similar levels (169 mg/dL versus 166 mg/dL, respectively). Prevalence of high cholesterol level (≥240 mg/dL) was very low (1.3%) in both men (2.2%) and women (0.5%). However, the prevalence of borderline high cholesterol was substantial (5.8%) in this sample.ConclusionThe prevalence of high hypercholesterolemia is low, whereas there is a high prevalence of borderline high cholesterol and diabetes in the adult population of Bangladesh. This warrants population-based interventions to tackle this problem.     

Impaired macrophage production of anti-atherosclerotic interleukin-10 induced by coronary intraplaque hemorrhage in patients with acute coronary syndrome and hyperglycemia

BackgroundCoronary intraplaque hemorrhage (IPH) accelerates atherosclerosis. Extracellular hemoglobin (Hb) released by IPH is cleared by macrophages with CD163 receptors. This process provokes secretion of the anti-atherosclerotic cytokine interleukin (IL)-10. The present study aimed to investigate the relationship between macrophage accumulation and IL-10 production provoked by IPH in plaques obtained from acute coronary syndrome (ACS) patients with hyperglycemia.MethodsIn 50 ACS patients, atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI). The debris was stained with antibodies to CD163, glycophorin A (GPA, a marker of IPH) and IL-10. %CD163 was defined as the ratios of CD163-positive cells to all cells. %IL-10 and %GPA were defined as the ratio of positively stained areas per total tissue area. Based on glycosylated Hb [HbA1c (NGSP)] ≥ 6.5%, fasting blood sugar (FBS) ≥ 126 mg/dL, and insulin resistance (HOMA-IR > 2.5), patients were divided into a diabetes mellitus (DM) group (N = 18, HbA1c ≥ 6.5% or FBS ≥ 126 mg/dL), an insulin resistance (IR) group (N = 15, HOMA-IR > 2.5, HbA1c < 6.5%, and FBS < 126 mg/dL), and a normal (NR) group (N = 17).ResultsCompared to the NR group, %GPA and %CD163 were increased in the DM and IR groups. %IL-10 was similar among the three groups. However, %IL-10/%CD163 ratios were decreased in the DM (2.5 ± 0.6, P = 0.01) and IR (2.7 ± 0.8, P = 0.02) groups compared to the NR group (5.8 ± 4.7). Only in the NR group was there a significant correlation between %IL-10 and %CD163.ConclusionsImpairment of the anti-inflammatory effect provoked by IPH contributes to premature atherosclerosis even in the IR group.     

Very-low-energy diet for type 2 diabetes: An underutilized therapy?

BackgroundCurrent approaches to the management of type 2 diabetes focus on the early initiation of novel pharmacologic therapies and bariatric surgery.ObjectiveThe purpose of this study was to revisit the use of intensive, outpatient, behavioral weight management programs for the management of type 2 diabetes.DesignProspective observational study of 66 patients with type 2 diabetes and BMI ≥ 32 kg/m² who enrolled in a program designed to produce 15% weight reduction over 12 weeks using total meal replacement and low- to moderate-intensity physical activity.ResultsPatients were 53 ± 7 years of age (mean ± SD) and 53% were men. After 12 weeks, BMI fell from 40.1 ± 6.6 to 35.1 ± 6.5 kg/m². HbA1c fell from 7.4% ± 1.3% to 6.5% ± 1.2% (57.4 ± 12.3 to 47.7 ± 12.9 mmol/mol) in patients with established diabetes: 76% of patients with established diabetes and 100% of patients with newly diagnosed diabetes achieved HbA1c < 7.0% (53.0 mmol/mol). Improvement in HbA1c over 12 weeks was associated with higher baseline HbA1c and greater reduction in BMI.ConclusionsAn intensive, outpatient, behavioral weight management program significantly improved HbA1c in patients with type 2 diabetes over 12 weeks. The use of such programs should be encouraged among obese patients with type 2 diabetes.     

Revisit frequency and its association with quality of care among diabetic patients: Translating Research Into Action for Diabetes (TRIAD)

ObjectiveTo describe patient and provider characteristics associated with outpatient revisit frequency and to examine the associations between the revisit frequency and the processes and intermediate outcomes of diabetes care.Research design and methodsWe analyzed data from Translating Research Into Action for Diabetes (TRIAD), a prospective, multicenter, observational study of diabetes care in managed care.ResultsOur analysis included 6040 eligible adult participants with type 2 diabetes (42.6% ≥ 65 years of age, 54.1% female) whose primary care providers were the main provider of the participants’ diabetes care. The median (interquartile range) revisit frequency was 4.0 (3.7, 6.0) visits per year. Being female, having lower education, lower income, more complex diabetes treatment, cardiovascular disease, higher Charlson comorbidity index, and impaired mobility were associated with higher revisit frequency. The proportion of participants who had annual assessments of HbA1c and LDL-cholesterol, foot examinations, advised or documented aspirin use, and influenza immunizations were higher for those with higher revisit frequency. The proportion of participants who met HbA1c (< 9.5%) and LDL-cholesterol (< 130 mg/dL) treatment goals were higher for those with a higher revisit frequency. The predicted probabilities of achieving more aggressive goals, HbA1c < 8.5%, LDL-cholesterol < 100 mg/dL, and blood pressure < 130/85 or even < 140/90 mmHg were not associated with higher revisit frequency.ConclusionsRevisit frequency was highly variable and was associated with both sociodemographic characteristics and disease severity. A higher revisit frequency was associated with better processes of diabetes care, but the association with intermediate outcomes was less clear.     

Vitamin D supplementation and glycemic control in type 2 diabetes patients: A systematic review and meta-analysis

IntroductionLow vitamin D status has been found to be associated with impaired glycemic control in patients who suffer from type 2 diabetes; however, whether vitamin D supplementation is associated with improved glycemic status remains controversial. The aim of this study was to summarize evidence from randomized controlled trials (RCTs) to assess the efficacy of vitamin D supplementation in reducing glycosylated haemoglobinA1c (HbA1c) and fasting blood glucose (FBG) levels.Materials/MethodsWe searched PubMed, Web of Science and the Cochrane Library for reports published up to March 2017. We selected parallel RCTs investigating the effect of vitamin D or vitamin D analogues on HbA1c or FBG levels in type 2 diabetes patients. Cohen's d was calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95%confidence intervals (CIs) were pooled using a random effects model.ResultsTwenty-four studies were included that evaluated HbA1c levels and 18 studies were included that evaluated FBG levels. Meta-analyses showed that vitamin D supplementation was associated with reduced HbA1c levels (standardized mean difference (SMD) − 0.25 [− 0.45 to − 0.05]) but had no influence on FBG levels (SMD − 0.14 [− 0.31 to 0.03]). However, the subgroup analyses suggested that vitamin D supplementation was associated with reduced HbA1c levels (SMD − 0.39 [− 0.67 to − 0.10]) and FBG (SMD − 0.27 [− 0.46 to − 0.07]) among patients with 25-hydroxyvitamin D (25(OH) D) deficiency at baseline. Significantly reduced HbA1c levels were also observed in association with vitamin D supplementation in the subgroup including type 2 diabetes patients with a body mass index (BMI) < 30 kg m^− 2 (SMD − 0.30 [− 0.54 to − 0.07]).ConclusionsVitamin D supplementation could be effective at improving glycemic control in vitamin D deficient or non-obese type 2 diabetes patients.     

Efficacy of lifestyle interventions in the reversion to normoglycemia in Korean prediabetics: One-year results from a randomised controlled trial

AimThis study aimed to determine the efficacy of personalized lifestyle interventions on the reversion of a prediabetic state to normoglycemia compared with regular blood glucose testing alone in prediabetes.MethodsA randomized, multicenter trial was conducted in prediabetes aged 30–70 with fasting blood glucose level of 5.6–6.9 mmol/L (100–125 mg/dL) and/or HbA1c level of 39–46 mmol/mol (5.7–6.4%) recruited from health checkups at 16 health-promotion centers in Korea. The 799 recruited individuals were randomized to either the personalized lifestyle intervention group (LIG) or the control group (CG) by a computer generated random number list prepared by an independent statistician. The CG was provided with fasting blood glucose and HbA1c tests alone every 3 months during the first year. The LIG was provided not only blood glucose test but five sessions of personalized lifestyle counseling by nutritionists every 3 months during the first year aimed at improving the diet, alcohol and exercise behaviors. Data from lifestyle assesments and laboratory measurements were analyzed at 1-year after baseline. The primary outcome was the reversion rate from prediabetes to normoglycemia. Additional outcome include the effect of the lifestyle intervention program on lifestyle changes in the LIG to support primary outcome.ResultsThe 799 participants randomly allocated to the LIG (n = 398) or the CG (n = 401). For the analyses of outcomes, 629 participants (313 men and 316 women; mean age, 53.7 ± 9.4 years; mean body mass index (BMI), 24.7 kg/m²) were included: 325 in the LIG; 304 in the CG. Diet (7.03, 95% CI = 4.56–10.86, P < 0.001), alcohol (2.24, 95% CI = 1.48–3.41, P < 0.001), and exercise behaviors (1.85, 95% CI = 1.31–2.63, P < 0.001) were improved relative to baseline by the personalized lifestyle intervention in the LIG after adjusting age, sex, and family history of diabetes. In terms of main outcome, the cumulative incidence of reversion from prediabetes to normoglycemia at the first year was 37.9% (123/325) [95% CI = 32.6–43.1%] in the LIG and 29.6% (90/304) (95% CI = 24.5–34.7%) in the CG. After adjustment for age, sex, family history of diabetes, BMI, blood pressure, and lipids, the hazard ratio for reverting to normoglycemia remained significantly higher in the LIG (1.40, 95% CI = 1.06–1.83, P = 0.017) than in the CG.ConclusionPersonalized lifestyle intervention could be more effective compared with regular blood glucose testing alone in the reversion of a prediabetic state to normoglycemia in Korean prediabetics. This finding suggests that diabetes prevention care would be benefited by incorporating personalized lifestyle counseling.This study was registered at cris.nih.go.kr (KCT0001580).     

Comparison of the effects of three angiotensin II receptor type 1 blockers on metabolic parameters in hypertensive patients with type 2 diabetes mellitus

ObjectiveIn a previous study involving 18 hypertensive patients with type 2 diabetes mellitus, we found that replacement of valsartan and candesartan by telmisartan significantly improved insulin sensitivity and significantly increased serum adiponectin levels in the patients. We investigated the effects of 3 angiotensin II type 1 receptor blockers (ARBs)—telmisartan, candesartan, and valsartan—on metabolic parameters in hypertensive patients with type 2 diabetes.MethodsA total of 308 hypertensive patients with diabetes were enrolled in our multicentre, randomized, open-label study. The patients received 40 mg telmisartan, 8 mg candesartan, or 80 mg valsartan for 3 months, and the data of 227 patients (telmisartan: n = 74, candesartan: n = 79, and valsartan: n = 74) were analysed.ResultsThe systolic and diastolic blood pressures significantly decreased in all the groups at the end of the study; the decrease was comparable among the 3 groups. The changes in fasting plasma glucose, fasting insulin, glycated haemoglobin (HbA1c), total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, adiponectin, free fatty acids, high-sensitivity C-reactive protein (hs-CRP), and plasminogen activator inhibitor-1 (PAI-1) were comparable between the 3 groups. Telmisartan and candesartan administration tended to lower urinary albumin excretion.ConclusionsLow dose telmisartan had a neutral effect on metabolic dysfunction in hypertensive patients with type 2 diabetes; the effect produced by 40 mg telmisartan was comparable with that of 8 mg candesartan and 80 mg valsartan. Failure to detect metabolic differences among the various ARB treatments could have been due to the low statistical power of the study design.     

Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin

BackgroundVulvovaginitis, balanitis, and related genital infections are common in patients with type 2 diabetes. Glucosuria, which is an outcome of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors, is among the possible causes. Dapagliflozin, an SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes, has been studied across a broad spectrum of patients. Analysis of multi-trial safety data may better define the relationship between glucosuria and genital infection.MethodsSafety data were pooled from 12 randomized, placebo-controlled Phase 2b/3 trials to analyze the association of glucosuria with genital infection in patients with suboptimally controlled diabetes (HbA1c > 6.5%–12%). Patients were randomized to receive dapagliflozin (2.5 mg, 5 mg, or 10 mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12–24 weeks. The incidence of clinical diagnoses and of events suggestive of genital infection was evaluated.ResultsThe pooled safety data included 4545 patients: 3152 who received once-daily dapagliflozin (2.5 mg [n = 814], 5 mg [n = 1145], or 10 mg [n = 1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5 mg, 5 mg, 10 mg, and placebo, diagnosed infections were reported in 4.1%, 5.7%, 4.8%, and 0.9%, respectively. Most infections were mild or moderate and responded to standard antimicrobial treatment. Discontinuation due to these events was rare. No clear dose–response relationship between dapagliflozin and genital infection was demonstrated.ConclusionsTreatment with dapagliflozin 2.5 mg, 5 mg, or 10 mg once daily is accompanied by an increased risk of vulvovaginitis or balanitis, related to the induction of glucosuria. Events were generally mild to moderate, clinically manageable, and rarely led to discontinuation of treatment.     

V-shaped relationship between HbA1c and all-cause mortality in the elderly with type 2 diabetes

PurposeThe optimal glycemic target for elderly patients with diabetes has not been established. The purpose of this study was to elucidate relationship between HbA1c and mortality in elderly patients with diabetes.SubjectsThree hundred consecutive elderly (≥ 65 yrs) patients with type 2 diabetes mellitus admitted for control of hyperglycemia between 2002 and 2010 were registered. Upon mortality survey at the end of 2012, 201 (70%) of them were traceable (men/women 121/80, mean age 71 yrs, duration of diabetes 11 yrs and HbA1c 9.9%). The analysis took account of the following baseline information: gender, age, duration of diabetes, HbA1c, body mass index, systolic blood pressure, eGFR, urinary albumin excretion, serum lipid levels and use of insulin and oral hypoglycemic agents. The follow-up HbA1c was also recorded.ResultsThe mean follow-up period was 5.7 yrs and 45 of the patients have died. The mortality hazard as a function of the baseline HbA1c quartile was significantly V-shaped with the nadir in quartile 2 (HbA1c 8.5–9.4%) (P = 0.02), and this relationship remained significant after adjustment for the confounders such as estimated glomerular filtration rate and insulin use. The follow-up HbA1c was 7.7 ± 1.6% and not significantly related to mortality.Discussion/ConclusionThere was a V-shaped relationship between baseline HbA1c and all-cause mortality in elderly patients with insufficiently controlled glycemia. The nadir was in Q2 in which the HbA1c value was 8.5–9.4%. No significant relationship was found between the follow-up HbA1c and mortality. Further studies are needed to clarify the relationship between HbA1c and mortality in the elderly.     

Perfil clínico de los pacientes tratados con evolocumab en unidades hospitalarias de nefrología en España (RETOSS-NEFRO)

Background and objectiveTo describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain.Material and methodsRetrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12 ± 4 weeks post-initiation of evolocumab were reviewed.ResultsSixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73 m² (51.7% of patients had eGFR < 60 ml/min/1.73 m² [CKD stage > 2]), 50.0% had proteinuria (>300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c≥160 mg/dL and 29.3%≥190 mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100 mg/dL, 70.0% <70 mg/dL, and 55.0% <55 mg/dL, while mean eGFR levels and statin use were remained stable.ConclusionIn Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.