Hypertension attenuates the link of osteoprotegerin to reduced baroreflex sensitivity in type 2 diabetes mellitus patients on oral antidiabetic and antihypertensive therapy - a cross sectional study.

PURPOSE: Decreased baroreflex sensitivity (BRS) has been shown to be a marker of cardiovascular (CV) risk. In the present study, the difference in CV risk biomarkers in type 2 diabetes (T2D) patients receiving oral antidiabetic drugs (OAD) with and without hypertension has been assessed. MATERIALS AND METHODS: Ninety-two T2D patients on OAD without hypertension (control group) and eighty-eight diabetic patients with hypertension on OAD and antihypertensive drugs (test group) matched for age, gender, body mass index, serum glucose, glycated haemoglobin, and duration of the disease were recruited for the study. Their blood pressure (BP) variability including BRS, heart rate variability (HRV), insulin, lipid profile, osteoprotegerin (OPG), and tumor necrosis factor-α (TNF-α) were estimated. The association of various factors with BRS was assessed by Spearman correlation and multiple regression analysis. RESULTS: BRS was decreased (13.90 ± 5.27 vs 6.76 ± 4.58), HRV sympathetic indices [LFnu, LF-HF ratio (1.30 ± 0.49 vs 1.93 ± 0.62)], HOMA-IR, atherogenic index of plasma (AIP), OPG (223.08 ± 103.86 vs 287.60 ± 121.36) and TNF-α were increased, and parasympathetic indices [TP (1012.90 ± 316.18 vs 625.88 ± 229.84), RMSSD, SDNN, NN50, pNN50] were decreased in the test group compared to control group. In control group, parasympathetic indices, AIP, OPG, and TNF-α had a significant correlation and OPG had an independent association (ß - 0.344; p 0.004) with BRS. In test group, BP, LF-HF ratio, parasympathetic indices, AIP, OPG, and TNF-α had significant correlation, and TNF-α alone (ß - 0.297; p 0.022) had an independent contribution to decreased BRS. CONCLUSION: Despite antidiabetic and antihypertensive treatments, T2D patients with hypertension had more cardiometabolic risks in comparison to normotensive T2D patients. Inflammation could be the inciting factor for rise in BP and decrease in BRS (CV risk) in hypertensive T2D patients. Hypertension in diabetes could attenuate the link of OPG to the reduction in BRS. Reduction in BRS could be a physiological marker of CV risk in T2D patients treated with OAD.

Decentralizing diabetes care from tertiary to primary care: how many persons with diabetes can be down-referred to primary care settings?

BACKGROUND: In a cohort of persons with diabetes (PWDs) seeking care at a tertiary care center, we aimed to determine the proportion of PWDs eligible and willing for down referral to primary health centers (PHCs). METHODS: We conducted a cross-sectional analytical study among PWDs on treatment for at least 1 year. PWDs with stable blood sugar, no history of cardiovascular events and proliferative retinopathy were considered as 'eligible' for primary care management. RESULTS: Of the total 1002 PWDs, mean (SD) age was 56 (12) years; 62% were male and 81% were from rural areas. About half (49%) of them were on insulin, and 52% had comorbidities. In total, 45.6% (95% CI: 42.3-48.8%) were eligible to be managed at PHCs. Among those who were eligible, 46.6% were willing to go back to PHCs. Males (APR = 1.16), people with diabetes for more than 10 years (APR = 1.23), and the presence of comorbidities (APR = 1.13) were significantly associated with unwillingness. Quality of medicines (46%) and poor facilities (40%) at PHCs were the main reasons for unwillingness. CONCLUSIONS: About half of the PWDs availing care at tertiary hospitals can be managed at primary care settings; of those, only half were willing to receive care at PHCs.

Association of rs2073618 polymorphism and osteoprotegerin levels with hypertension and cardiovascular risks in patients with type 2 diabetes mellitus.

There are reports of link of osteoprotegerin (OPG) gene polymorphism to type-2 diabetes (T2D) and hypertension (HTN). The objective of the study was to assess the allele frequency of OPG (rs2073618) gene polymorphism and its association with heart rate variability (HRV) and blood pressure variability profile as CVD risks in diabetes mellitus patients with hypertension undergoing treatment. T2D patients on treatment without hypertension (n = 172), with hypertension (n = 177) and 191 healthy volunteers were recruited for the study. Their blood pressure variability including baroreflex sensitivity (BRS), heart rate variability (HRV), OPG, insulin, lipid profile, receptor-activator for NFkB (RANK), receptor-activator for NFkB-Ligand (RANKL), and tumor necrosis factor-α (TNF-α) were estimated. Allele frequency of OPG (rs2073618) gene polymorphism was assessed from the DNA samples. BRS and HRV indices were decreased, and RANKL/OPG and TNF-α were increased in T2D and T2D + HTN groups, respectively compared to healthy control group. The reduction in BRS was contributed by increased inflammation and reduced SDNN of HRV in GG genotype in T2D + HTN. In GG + GC subgroup, it was additionally contributed by rise in RANKL/OPG level (ß - 0.219; p 0.008). Presence of mutant GG genotype contributed to the risk of hypertension among T2D patients (OR 3.004) as well as in general population (OR 2.79). It was concluded that CV risks are more in T2D patients with HTN expressing OPG rs2073618 gene polymorphism.

Down referral and assessing comprehensive diabetes care in primary care settings: An operational research from India.

BACKGROUND AND AIMS: In this study, we aimed to refer eligible (patients with stable blood sugar and without any history of cardiovascular events or proliferative retinopathy) and willing persons with diabetes (PwDs) to primary healthcare centers (PHCs) from tertiary care and to compare the care indicators. METHODS: This before-after interventional study was conducted among PwDs aged ≥18 years at a tertiary care hospital in South India. Care indicators (regularity to the clinic, waiting time, and blood sugar control status) were assessed before down referral and after three months of follow-ups at PHCs. RESULTS: Of 204 PwDs referred to PHCs. Among them, 88% (n = 180) registered at PHCs for care and 46% (n = 94, 95% CI 39.1-53.2%) were lost to follow-ups at PHCs. The main reason for loss to follow-ups was the unavailability of medicines at PHCs(n = 41, 44%). Among those who were on regular follow-ups at PHCs, there was no significant difference in fasting blood glucose (FBG) control status compared to tertiary (52%-64.6%, p = 0.083). However, there was a significant improvement in the regularity of clinic visits (75% vs. 100%, p < 0.001), consultation waiting time (90 vs. 60 min, p = 0.028), and waiting time at pharmacy queues (120 vs. 30 min, p < 0.001) between tertiary care and PHCs. However, among those registered at PHCs, only 40.6% (n = 73, 95% CI 33.3-48.1) were willing to continue care at PHCs for their diabetes management. CONCLUSION: Primary care was better than tertiary care in terms of PwD's regularity of clinic visits and waiting time for care.

Effect of COVID19 pandemic and national lockdown on persons with diabetes from rural areas availing care in a tertiary care center, southern India.

BACKGROUND AND AIMS: COVID-19 pandemic and lockdown measures to contain it have affected health care services globally. This study aims to assess the effect and urban-rural differences of COVID19 pandemic on diabetes care. METHODS: This cross-sectional study was conducted among persons with diabetes (PWDs) registered for care at a diabetes clinic of a tertiary care center in Southern India. We collected following information by telephonic interviews: physician consultations, access to diabetes medications and blood sugar tests, use of telemedicine services, out of pocket expenditure and psychological morbidity. RESULTS: A total of 350 PWDs were interviewed. Majority were male (78%) and from rural areas (79%). One fourth (24%) met any physician for diabetes care at least once during lockdown. PWDs from rural areas mainly consulted a physician in a private clinic (55%) compared to urban areas (26%). Two third (65%) availed medications from private medical shops. Almost half (46%) got their blood sugar tested during and majority of them (81%) reported unsatisfactory glycemic control. Only few (5%) was aware and three utilized telemedicine services. Almost all (99%) spent money (US $ 8.3) for diabetes care. One third (33%) had moderate or high psychological distress. CONCLUSIONS: Majority of PWDs did not consult a physician during lockdown. Cost of care was high. Measures to improve utilisation of telemedicine services and peripheral health facilities are needed.

Immunophenotypic and intracellular cytokine profile of Indian patients with tuberculosis with and without human immunodeficiency virus co-infection.

BACKGROUND: Tuberculosis (TB) occurs in more than 50% of human immunodeficiency virus (HIV) infected Indian patients. This study was carried out to determine the immunophenotypic and intracellular cytokine profile of patients with HIV-TB co-infection. PATIENTS AND METHODS: Fifteen patients with HIV-TB co-infection and 15 each with TB alone and healthy individuals were studied. Immunophenotypic analysis and intracellular cytokines were measured using appropriate antibodies on a flowcytometer. RESULTS: Percentage of CD3+ did not differ significantly in the three groups. The ratio of CD4+ : CD8+ was reversed among patients with TB and HIV-TB. CD19+ and CD25+ were present on fewer cells of healthy individuals but this was not statistically significant. Significantly higher percentage of cells of patients with TB and HIV-TB were CD69 positive. Interferon-gamma (INF-gamma) and tumour necrosis factor-alpha (TNF-alpha) levels are significantly reduced in the CD4+ cells of patients with HIV-TB when compared with those with TB and healthy individuals. In CD8+ cells of patients with HIV-TB, levels of TNF-alpha are higher when compared with the other two groups. Interleukin-2 (IL-2) producing cells were not significantly different in any of the above subsets. Monocytes in individuals with HIV-TB had significantly higher interleukin-6 (IL-6) and TNF-alpha. CONCLUSIONS: T-helper cells among patients with HIV-TB have significantly lower cytokine production. T-suppressor cells and monocytes produce more TNF-alpha. These findings may be significant in view of recent attempts to treat HIV-TB coinfected patients with anti-TNF therapy.