Coprevalence of type 2 diabetes mellitus and tuberculosis in low‐income and middle‐income countries: A systematic review

Increasing coprevalence of diabetes mellitus (DM) and tuberculosis (TB) in low‐income and middle‐income countries (LMICs) indicates a rising threat to the decades of progress made against TB and requires global attention. This systematic review provides a summary of type 2 diabetes and tuberculosis coprevalence in various LMICs. We searched PubMed, Ovid Medline, Embase, and PsychINFO databases for studies that provided estimates of TB‐DM coprevalence in LMICs published between 1990 and 2016. Studies that were non‐English and exclusively conducted in multidrug resistant‐tuberculosis or type 1 diabetes and inpatient settings were excluded. We reviewed 84 studies from 31 countries. There were huge diversity of study designs and diagnostic methods used to estimate coprevalence, and this precluded pooling of the results. Most studies (n = 78) were from small, localized settings. The DM prevalence among TB patients in various LMICs varied from 1.8% to 45%, with the majority (n = 44) between 10% and 30%. The TB prevalence among people with DM ranged from 0.1% to 6.0% with most studies (n = 9) reporting prevalences less than 2%. Coprevalence of TB‐DM was higher than general population prevalence of either diseases in these countries. This study underscores the need for intervention and more focused research on TB DM bidirectional screening programs in low‐income and middle‐income countries as well as integrated chronic disease management.     

Women living with HIV in high‐income settings and breastfeeding

Guidelines in high‐income settings recommend breastfeeding avoidance amongst women living with HIV (WLWH). Increasingly, WLWH in high‐income settings, who are well‐treated with fully suppressed viral loads, are choosing to breastfeed their infants, even with these recommendations. The purpose of this article is to review existing research and guidance on infant feeding amongst WLWH in high‐income countries and to identify gaps in this evidence that require further investigation. Current evidence on the risk of HIV transmission through breastfeeding in the context of antiretroviral therapy (ART), the significance of cell‐associated virus, transmission risk factors, retention in care and adherence postpartum, infant prophylaxis and antiretroviral exposure, and monitoring of the breastfeeding WLWH are summarized. A latent HIV reservoir is persistently present in breast milk, even in the context of ART. Thus, suppressive maternal ART significantly reduces, but does not eliminate, the risk of postnatal transmission of HIV. There are currently limited data to guide the optimal frequency of virologic monitoring and the clinical actions to take in case of maternal detectable viral load whilst breastfeeding. Moreover, retention in care and adherence to ART in the postpartum period may be difficult and more research is needed to understand what clinical and psychosocial support would benefit these mothers so that successful engagement in care can be achieved. The long‐term effects of antiretroviral drug exposure in the infants also need further exploration. Thus, there is a need for collecting enhanced surveillance data on WLWH who breastfeed and their infants to augment clinical guidance in high‐income settings.     

Effects of patient‐tailored atorvastatin therapy on ameliorating the levels of atherogenic lipids and inflammation beyond lowering low‐density lipoprotein cholesterol in patients with type 2 diabetes

Aims/Introduction

Recently, patient‐tailored statin therapy was proven effective for achieving target low‐density lipoprotein (LDL) cholesterol levels. It is unclear, however, whether this therapeutic modality would be effective for atherogenic lipid profiles and inflammation in patients with type 2 diabetes.

Materials and Methods

The present study was an 8‐week, multicenter, single‐step titration trial of patient‐tailored atorvastatin therapy (10, 20 and 40 mg) according to baseline LDL cholesterol levels in 440 patients with type 2 diabetes. We measured the LDL particle size by polyacrylamide gel electrophoresis, and used high‐sensitivity C‐reactive protein (hsCRP) and adiponectin as surrogate markers of inflammation.

Results

In the intention‐to‐treat analysis, 91% of the patients achieved their LDL cholesterol targets (<2.6 mmol/L) at week 8. There were significant reductions at week 8 in total cholesterol, triglycerides, non‐high‐density lipoprotein cholesterol (HDL) cholesterol, and the total cholesterol:HDL cholesterol ratio compared with the baseline values for all of the doses. The mean LDL particle size was significantly increased, and the small, dense LDL cholesterol levels were decreased in a dose‐dependent manner over the study period. In addition, the hsCRP levels were decreased in those high‐risk patients with baseline hsCRP levels over 3 mg/L (P < 0.001), and the adiponectin levels tended to increase with all of the doses (P = 0.004) at 8 weeks.

Conclusions

Patient‐tailored atorvastatin therapy based on LDL cholesterol at baseline was effective in ameliorating atherogenic LDL particle size and inflammation, in addition to achieving the target LDL cholesterol level without an undesirable effect on glycemic control in patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT01239849).     

Effect of peer education on self‐management and psychological status in type 2 diabetes patients with emotional disorders

Aims/Introduction

The purpose of the present study was to assess the effect of peer education in type 2 diabetes patients with emotional disorders on the metabolic index and psychological status.

Materials and Methods

Educators use psychological scales to screen type 2 diabetes patients with emotional disorders. Participants were divided into usual and peer education groups. Both groups received usual diabetes education. Peer leaders were recruited to provide support with the peer education group for 6 months. The metabolic index, diabetes knowledge, self-management, diabetes-related distress, emotional status and quality of life were compared at the end of the study.

Results

A total of 127 patients participated in the study. There were 20 peer leaders engaged in the study as volunteers for peer education. All participants completed the study and fulfilled the scales. Improvements in the peer education group were significant compared with the usual education group with respect to anxiety (49.0 ± 9.65 vs 54.0 ± 8.48), depression (51.3 ± 7.97 vs 55.8 ± 7.52), diabetes knowledge (18.8 ± 2.46 vs 16.3 ± 2.08), distress (2.67 ± 0.55 vs 3.02 ± 0.56), self-management (66.5 ± 4.26 vs 62.4 ± 5.88) and quality of life (−1.98 ± 0.82 vs −2.50 ± 0.71), whereas no significant difference existed with respect to the metabolic index.

Conclusions

Peer education, providing more attention to diabetes patients with emotional disorders, is a preferred model for delivering care.     

Pan‐genotypic treatment regimens for hepatitis C virus: Advantages and disadvantages in high‐ and low‐income regions

During the last 5 years, the availability of direct‐acting antiviral (DAA) agents has revolutionized the treatment of hepatitis C virus (HCV). Compared with interferon/ribavirin—the previous standard of care—DAA combination regimens offer improved sustained virological response (SVR) rates, shorter treatment durations of 8‐24 weeks, convenient once‐daily single‐tablet formulations and more favourable tolerability profiles. HCV treatment is complex, and the choice of therapy must consider a complex range of factors, including baseline viral load, fibrosis stage, the HCV genotype and subgenotype, and the presence of resistance‐associated substitutions at baseline. Globally, HCV genotype 1 predominates, and there are extensive data and various treatment options available for this genotype. Genotypes 2–6 are prevalent and may even predominate in different geographical regions, reflecting diverse factors including human migration patterns and unsafe use of injection drugs and blood products. Such factors are themselves influenced by socio‐economic factors, and poor regions often have the greatest unmet need for effective HCV therapies. The latest pan‐genotypic DAA combination regimens provide the potential to eradicate HCV around the globe, regardless of genotype, hence minimizing the need for virological testing services, which often are unavailable in poorer regions. Economics inevitably remain a barrier to access, and extensive cooperation will be required between clinical organisations and pharmaceutical manufacturers to agree appropriate pricing policies, especially in poorer economic regions. This review considers key data and treatment guidelines for DAA therapies, including pan‐genotypic combination regimens, in the context of regional differences in HCV genotype and socio‐economic factors.     

Maternal body mass index and risk of birth and maternal health outcomes in low‐ and middle‐income countries: a systematic review and meta‐analysis

We conducted a systematic review and meta‐analysis of population‐based cohort studies of maternal body mass index (BMI) and risk of adverse birth and health outcomes in low‐ and middle‐income countries. PubMed, Embase, CINAHL and the British Nursing Index were searched from inception to February 2014. Forty‐two studies were included. Our study found that maternal underweight was significantly associated with higher risk of preterm birth (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01–1.27), low birthweight (OR, 1.66; 95% CI, 1.50–1.84) and small for gestational age (OR, 1.85; 95% CI, 1.69–2.02). Compared with mothers with normal BMI, overweight or obese mothers were at increased odds of gestational diabetes, pregnancy‐induced hypertension, pre‐eclampsia, caesarean delivery and post‐partum haemorrhage. The population‐attributable risk (PAR) indicated that if women were entirely unexposed to overweight or obesity during the pre‐pregnancy or early pregnancy period, 14% to 35% fewer women would develop gestational diabetes, pre‐eclampsia or pregnancy‐induced hypertension in Brazil, China, India, Iran or Thailand. The highest PAR of low birthweight attributable to maternal underweight was found in Iran (20%), followed by India (18%), Thailand (10%) and China (8%). Treatment and prevention of maternal underweight, overweight or obesity may help reduce the burden on maternal and child health in developing countries.     

Comparison of three α‐glucosidase inhibitors for glycemic control and bodyweight reduction in Japanese patients with obese type 2 diabetes

Aims/Introduction

α‐Glucosidase inhibitors (αGIs) are widely used for the primary treatment of type 2 diabetes. We compared the clinical effects of three αGIs (miglitol, acarbose and voglibose) in patients with obese type 2 diabetes.

Materials and Methods

Japanese patients (n = 81) with obese type 2 diabetes (body mass index [BMI] ≥25 kg/m²) were enrolled in this multicenter, open‐label study. The participants were randomized into the miglitol (n = 18), acarbose (n = 22), voglibose (n = 19) or control (n = 22) groups. Glycemic control (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI, serum insulin, serum lipids (low‐density lipoprotein and high‐density lipoprotein cholesterol, and triacylglycerols) and adipocytokines (leptin and adiponectin) were evaluated every 4 weeks for 12 weeks.

Results

In the miglitol group, HbA1c was improved significantly from the baseline at all points. The changes in HbA1c at 8 and 12 weeks from baseline were greater in the miglitol group than the control group. The voglibose group showed significant improvements in HbA1c at 12 weeks. Bodyweight and BMI were decreased significantly in the miglitol group. In addition, significant correlations were observed between the decrements in HbA1c and bodyweights over 12 weeks in the miglitol (r = 0.759, P < 0.001) and voglibose groups (r = 0.667, P = 0.002). Serum lipid and adipocytokine levels were not altered in any groups.

Conclusions

αGIs, especially miglitol, can effectively control blood glucose and bodyweight in obese type 2 diabetes. This study was registered with UMIN (no. UMIN000006465).     

Identification of novel risk genes associated with type 1 diabetes mellitus using a genome‐wide gene‐based association analysis

Aims/Introduction

Type 1 diabetes mellitus is a serious disorder characterized by destruction of pancreatic β-cells, culminating in absolute insulin deficiency. Genetic factors contribute to the susceptibility of type 1 diabetes mellitus. The aim of the present study was to identify more susceptibility genes of type 1 diabetes mellitus.

Materials and Methods

We carried out an initial gene-based genome-wide association study in a total of 4,075 type 1 diabetes mellitus cases and 2,604 controls by using the Gene-based Association Test using Extended Simes procedure. Furthermore, we carried out replication studies, differential expression analysis and functional annotation clustering analysis to support the significance of the identified susceptibility genes.

Results

We identified 452 genes associated with type 1 diabetes mellitus, even after adapting the genome-wide threshold for significance (P < 9.05E-04). Among these genes, 171 were newly identified for type 1 diabetes mellitus, which were ignored in single-nucleotide polymorphism-based association analysis and were not previously reported. We found that 53 genes have supportive evidence from replication studies and/or differential expression studies. In particular, seven genes including four non-human leukocyte antigen (HLA) genes (RASIP1, STRN4, BCAR1 and MYL2) are replicated in at least one independent population and also differentially expressed in peripheral blood mononuclear cells or monocytes. Furthermore, the associated genes tend to enrich in immune-related pathways or Gene Ontology project terms.

Conclusions

The present results suggest the high power of gene-based association analysis in detecting disease-susceptibility genes. Our findings provide more insights into the genetic basis of type 1 diabetes mellitus.     

The relationship between the frequency of self‐monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections

Aims/Introduction

We investigated the relationship between the frequency of self-monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software.

Materials and Methods

We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNET™ SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients'' hemoglobin A1c (HbA1c) levels was analyzed using the χ²-test and linear regression analysis was carried out to clarify their relationship.

Results

The odds ratio of achieving a target HbA1c level of <8% (63.9 mmol/mol) was significantly higher in subjects with SMBG frequencies of ≥3.5 times/day compared with those with SMBG frequencies of <3.5 times/day in the CSII group (odds ratio 7.00, 95% confidence interval 1.72–28.54), but not in the MDI group (odds ratio 1.35, 95% CI 0.62–2.93). A significant correlation between SMBG frequency and the HbA1c level was detected in the CSII group (HbA1c [%] = –0.24 × SMBG frequency [times/day] + 8.60 [HbA1c {mmol/L} = –2.61 × SMBG frequency {times/day} + 70.5], [r = –0.384, P = 0.012]), but not in the MDI group.

Conclusions

A SMBG frequency of <3.5 times per day appeared to be a risk factor for poor glycemic control (HbA1c ≥8%) in type 1 diabetes mellitus patients on CSII.     

Challenges in achieving optimal glycemic control in type 2 diabetes patients with declining renal function: The Southeast Asia perspective

It is well recognised that Asia is at the epicenter of the global type 2 diabetes epidemic. Driven by socioeconomic changes involving industrialization, urbanization and adoption of Western lifestyles, the unprecedented increases in the prevalence of diabetes are particularly evident in Southeast Asia. The impact of diabetes is immense, and despite evidence of the benefit of optimal glucose control in reducing the risk of disease progression and development of macrovascular and microvascular complications, many individuals in this region remain poorly controlled. Chronic kidney disease (CKD) is an increasingly common diabetes‐associated complication in Asian patients. Furthermore, Southeast Asia has one of the highest rates of end‐stage renal disease (ESRD) in the world. Consequently, CKD in diabetes is associated with considerable morbidity and cardiovascular‐related mortality, highlighting the need to screen and assess patients early in the course of the disease. The management of type 2 diabetes patients with declining renal function represents a significant challenge. Many of the older antidiabetic agents, such as metformin and sulfonylureas, are limited in their utility in CKD as a result of contraindications or hypoglycemic episodes. In contrast, dipeptidyl‐peptidase IV inhibitors have provided a welcome addition to the therapeutic armamentarium for achieving glycemic control in these special populations. With comparable efficacy to and more favorable pharmacokinetic and side‐effect profiles than traditional therapies, agents in this drug class, such as linagliptin, offer a more tailored approach to disease control in type 2 diabetes patients with declining renal function.     

Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

We investigated the efficacy and safety of repaglinide as an add‐on therapy for Japanese patients with type 2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500 mg/day, mainly) in addition to diet and exercise.

Materials and methods

In the 16‐week multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group trial (the phase III study), patients with type 2 diabetes mellitus with metformin monotherapy were randomly assigned to the repaglinide or placebo group. Thereafter, a 36‐week, multicenter, uncontrolled, dose‐titration method study was extended to a total duration of 52 weeks (the long‐term study). The primary end‐point of each study was a change in glycated hemoglobin (HbA_1c) from baseline.

Results

After 16 weeks, mean reductions in HbA_1c were significantly greater for the repaglinide group than for the placebo group (–0.98 ± 0.72% vs 0.13 ± 0.63%, P < 0.001). In the long‐term study, the mean change in HbA_1c was −0.76 ± 0.83%. The rate of adverse events was 60.6 and 50.0% in the repaglinide and placebo groups, respectively, in the phase III study, and 78.3% in the long‐term study. Hypoglycemia was reported in 11.7, 0 and 13.3% of patients in the repaglinide group, placebo group and long‐term study, respectively.

Conclusions

Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA_1c at week 16 and in a significant long‐term improvement in HbA_1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with JapicCTI (nos. JapicCTI‐101202 and JapicCTI‐101203).