Viveka P Jyotsna

Cardiac autonomic function in patients with diabetes improves with practice of comprehensive yogic breathing program

Background: The aim of this study was to observe the effect comprehensive yogic breathing (Sudarshan Kriya Yoga [SKY] and Pranayam) had on cardiac autonomic functions in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 64 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program. Standard therapy included dietary advice, brisk walking for 45 min daily, and administration of oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to the participants through a course of 12 h spread over 3 days. It was an interactive session in which SKY, a rhythmic cyclical breathing, preceded by Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic function tests were done before and after 6 months of intervention. Results: In the intervention group, after practicing the breathing techniques for 6 months, the improvement in sympathetic functions was statistically significant (P 0.04). The change in sympathetic functions in the standard therapy group was not significant (P 0.75). Parasympathetic functions did not show any significant change in either group. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P 0.06). In the standard therapy group, no change in cardiac autonomic functions was noted (P 0.99). Conclusion: Cardiac autonomic functions improved in patients with diabetes on standard treatment who followed the comprehensive yogic breathing program compared to patients who were on standard therapy alone.

Comprehensive yogic breathing program improves quality of life in patients with diabetes.

Objective: To assess the effect of a comprehensive yogic breathing program on glycemic control and quality of life (QOL) in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Patients having HbA1c between 6 and 9% for at least 3 months with lifestyle modification and oral antidiabetic medication were included. They were followed-up and randomized at 6 months into two groups: one group receiving standard treatment of diabetes and the other group receiving standard treatment of diabetes and taught and told to regularly practice the comprehensive yogic breathing program (Sudarshan Kriya Yoga and Pranayam). Change in fasting and post-prandial blood sugars, glycated hemoglobin and QOL as assessed by the World Health Organization QOL WHOQOL BREF questionnaire were assessed. Results: There was a trend toward improvement in glycemic control in the group practicing the comprehensive yogic breathing program compared with the group following standard treatment alone, although this was not significant. There was significant improvement in physical, psychological and social domains and total QOL post-intervention in the group practicing the comprehensive yogic breathing program as compared with the group following standard treatment alone. Conclusion: There was significant improvement in the QOL and a non-significant trend toward improvement in glycemic control in the group practicing the comprehensive yogic breathing program compared with the group that was following standard treatment alone.

Prevalence and pattern of cardiac autonomic dysfunction in newly detected type 2 diabetes mellitus

Cardiac autonomic functions were assessed in 145 consecutive recently detected type 2 diabetics. Ninety-nine healthy persons served as controls. Criteria for normalcy were, heart rate variation during deep breathing >or=15 beats/min, deep breathing expiratory to inspiratory R-R ratio >or=1.21, Valsalva ratio >or=1.21, sustained handgrip test >or=16 mm of mercury, cold pressor test >or=10, BP response to standing <or=10mm of mercury and 30:15 R-R ratio on standing >or=1.04. An abnormal test was defined as the above parameters being <10 beats/min, <1.21, <1.21, <or=10mm of mercury, <10, >or=30 mm of mercury and <or=1.0, respectively. A borderline test was defined as, heart rate variation during deep breathing 11-14, sustained handgrip test 11-15 mm of mercury, BP response to standing 11-29 mm of mercury and 30:15 R-R ratio on standing 1.01-1.03. Parasympathetic dysfunction was found in 44.2% and sympathetic dysfunction in 51.9% diabetics. Among healthy controls, these figures were 11.9% and 22.1%, respectively. Cardiac autonomic function was normal in 7.8% patients and 32.5% healthy controls.

Decreased autonomic modulation of heart rate and altered cardiac sympathovagal balance in patients with Cushing's syndrome: role of endogenous hypercortisolism.

Background/Aims: Endogenous Cushings syndrome is associated with a higher risk of cardiovascular morbidity and mortality. Previous literature suggested multiple possible links by which hypercortisolism may alter the autonomic control of cardiovascular functions. We investigated the impact of chronic endogenous hypercortisolism on the autonomic regulation of cardiac functions by short-term heart rate variability analysis. Methods: Eighteen patients with endogenous Cushings syndrome and 20 age-, gender- and BMI-matched controls participated in the study. ECG signal was acquired in lead II configuration for 5 min and heart rate variability assessment was made in both time and frequency domain using the extracted RR interval data. Results: All time and frequency domain measures of heart rate variability were significantly (p < 0.05) lower in the patient group compared to the control group. The patient group had an altered sympathovagal balance with low frequency/high frequency band ratio significantly higher than the control group [1.857 (0.6747-2.610) vs. 0.8581 (0.4779-1.352); p = 0.0253]. A significant negative correlation was obtained between normalized high frequency power of heart rate variability and basal cortisol levels (r = -0.6594; p = 0.0029). Multiple linear regression analysis identified age, disease duration (in months), basal cortisol levels and systolic blood pressure as independent predictors of normalized high frequency power. Conclusion: Findings of the study clearly portrayed the diminished autonomic modulation of heart rate in endogenous Cushings syndrome and its possible relationship with hypercortisolism as the main causative factor. Diminished heart rate variability may be an indicator of the increased risk of cardiac mortality in these patients.

Comparison of Gliclazide with Insulin as Initial Treatment Modality in Newly Diagnosed Type 2 Diabetes

AIM This study was designed to compare effectiveness and remission rate between gliclazide and insulin as initial treatment in newly diagnosed, drug-naive patients with type 2 diabetes. METHODS Newly diagnosed, drug-naive subjects with type 2 diabetes having mean fasting blood glucose >200 mg/dL were enrolled into either of two groups (gliclazide or insulin). The former received gliclazide modified-release 60 mg daily, while the insulin group received 16 units of premixed insulin as two divided doses along with medical nutrition therapy. Premeal blood glucose was monitored, and the dose was adjusted accordingly. Glycosylated hemoglobin (HbA1c), lipid profile, and postmeal C-peptide were estimated at baseline and 6 months. Remission was defined as euglycemia off drug for a minimum duration of 1 month. RESULTS Baseline and 6-month blood glucose, HbA1c, and lipid profile were comparable between groups. Blood glucose levels normalized in 2-6 weeks in both groups. At 6 months, one of 30 (3.33%) in the gliclazide group and 24 of 30 (80%) in the insulin group were in remission. Ten of 16 (62.5%) in the insulin group and one of 20 (.5%) in the gliclazide group continued to maintain euglycemia off all pharmacological treatment at 12 months. At 6 months, C-peptide increased in the insulin group (3.21+/-1.61 ng/mL at baseline vs. 5.82+/-2.23 ng/mL at 6 months), while it remained unchanged in the gliclazide group (3.4+/-1.87 ng/mL at baseline vs. 3.82+/-1.78 ng/mL at 6 months) (P=0.0003). CONCLUSIONS Comparable glycemic control could be achieved with both insulin and oral hypoglycemic agent in newly diagnosed type 2 diabetes subjects. Insulin treatment exceeded gliclazide in the remission (drug-free) rate.

Bone mineral density in patients of Graves disease pre- & post-treatment in a predominantly vitamin D deficient population.

Background & objectives: Hyperthyroidism causes bone loss, and its treatment may restore bone mass, however, concomitant vitamin D deficiency may prevent this. We undertook this study to measure the bone mineral density (BMD) 25 (OH) vitamin D levels in patients with Graves disease in our population which is predominently vitamin D deficient and how we change with when patients become euthyroid. Methods: The biochemical, thyroid functions, serum vitamin D levels and BMD were estimated in 80 consecutive patients with Graves and 80 euthyroid controls. Patients were treated and rendered euthyroid. Fifty four completed one year, and 27 completed two years of follow up. Results: Patients had significant reduced BMD during hyperthyroid state compared to normal healthy controls. The mean vitamin D levels at baseline were in the insufficient range both patients (12.67±6.24 ng/ml) and controls (10.99±7.05 ng/ml). The BMD improved at all sites with antithyroid treatment. But, the BMD adjusted for body mass index (BMI) and age at all sites showed significant decrease with time. Interpretation & conclusions: Age and body mass index positively correlated with BMD. There was improvement in absolute BMD of patients at one and two years of follow up. When the BMD was adjusted for age and BMI, there was a decrease in BMD at one year which was less in the second year including that the damage in BMD caused by thyroid hormone excess is not made up even after two years of patient being euthyroid. Whether vitamin D replacement would change this needs to be studied.

Completion report: Effect of Comprehensive Yogic Breathing program on type 2 diabetes: A randomized control trial.

Background: Yoga has been shown to be beneficial in diabetes in many studies, though randomized control trials are few. The aim of this randomized control trial was to see the effect of Sudarshan Kriya and related practices (comprehensive yogic breathing program) on quality of life, glycemic control, and cardiac autonomic functions in diabetes. Diabetes mellitus is a risk factor for sudden cardiac death. Cardiac autonomic neuropathy has been implicated in the causation of sudden cardiac death. Therefore, a maneuver to prevent progression of cardiac autonomic neuropathy holds significance. Materials and Methods: A total of 120 patients of diabetes on oral medication and diet and exercise advice were randomized into two groups: (1) Continued to receive standard treatment for diabetes. (2) Patients administered comprehensive yogic breathing program and monitored to regularly practice yoga in addition to standard treatment of diabetes. At 6 months, quality of life and postprandial plasma glucose significantly improved in the group practicing yoga compared to baseline, but there was no significant improvement in the fasting plasma glucose and glycated hemoglobin. Results: On per protocol analysis, sympathetic cardiac autonomic functions significantly improved from baseline in the group practicing comprehensive yogic breathing. Conclusion: This randomized control trial points towards the beneficial effect of yogic breathing program in preventing progression of cardiac neuropathy. This has important implications as cardiac autonomic neuropathy has been considered as one of the factors for sudden cardiac deaths.

Recovery of β-Cell Functions with Low-Dose Insulin Therapy: Study in Newly Diagnosed Type 2 Diabetes Mellitus Patients

AIM Insulin therapy induces remission in subjects with newly diagnosed type 2 diabetes mellitus (T2DM). This study assessed the insulin and C-peptide levels in newly diagnosed T2DM subjects during low-dose insulin therapy. SUBJECTS AND METHODS Twenty newly diagnosed, drug-naive, T2DM patients without acute or chronic complications were the subjects for this study. Premixed insulin (70/30), 16 units, as two divided doses, was started for all subjects after preliminary investigations. The same dose of insulin was continued until normoglycemia was achieved. Subsequently the insulin dose was down-titrated. Plasma insulin, C-peptide, and blood glucose (both fasting and after breakfast) were measured at baseline and monthly for 6 months. Body weight and glycosylated hemoglobin (HbA1c) were measured every 3 months and the lipid profile was obtained at baseline and at 6 months. RESULTS Blood glucose levels showed a rapid decreasing trend and reached the near-normoglycemic range by 3 months, whereas plasma insulin and C-peptide showed a slow and steady increase until the fourth month and remained the same during the next 2 months of follow-up. HbA1c was 11.3 ± 1.4% (range, 8.6-13.5%) and 7.05 ± 0.54% (range, 6.3-8.1%) at the time of diagnosis and at the end of 6 months, respectively. The mean weights of the study subjects at baseline and 3 and 6 months were 70 ± 16 kg (range, 44-95 kg), 68 ± 13 kg, and 68 ± 13 kg (P = 0.083), respectively. Total cholesterol, low-density lipoprotein-cholesterol, and triglycerides decreased, whereas high-density lipoprotein-cholesterol was higher at 6 months. CONCLUSION Low-dose insulin therapy in newly diagnosed T2DM leads to β-cell recovery (as documented by plasma insulin and C-peptide levels) by 3-4 months.

Effect of Cushing's syndrome — Endogenous hypercortisolemia on cardiovascular autonomic functions

Cushings syndrome is associated with increased cardiovascular morbidity and mortality. Its also associated with other cardiac risk factors like hypertension, diabetes mellitus and obesity. Cardiovascular autonomic function impairment could predict cardiovascular morbidity and mortality. Twenty five patients with Cushings syndrome without diabetes and twenty five age matched healthy controls underwent a battery of cardiovascular autonomic function tests including deep breath test, Valsalva test, hand grip test, cold pressor test and response to standing from lying position. The rise in diastolic blood pressure on hand grip test and diastolic BP response to cold pressor test in Cushings patients were significantly less compared to healthy controls (9.83 ± 3.90 vs 20.64 ± 9.55, p<0.001 and 10.09 ± 4.07 vs 15.33 ± 6.26, p<0.01 respectively). The E:I ratio on deep breathing test was also less in the patients in comparison to controls (1.36 ± 0.21 vs 1.53 ± 0.19, p<0.01). Seven patients underwent the same battery of tests 6 months after a curative surgery showing a trend towards normalization with significant improvement in expiratory to inspiratory ratio and sinus arrhythmia delta heart rate. To conclude, this study showed that chronic endogenous hypercortisolism in Cushings is associated with an impaired sympathetic cardiovascular autonomic functioning. After a curative surgery, some of the parameters tend to improve.

Identification of novel GHRHR and GH1 mutations in patients with isolated growth hormone deficiency

OBJECTIVE Human growth is an elementary process which starts at conception and continues through different stages of development under the influence of growth hormone (GH) secreted by the anterior pituitary gland. Variation affecting the production, release and functional activity of GH leads to growth hormone deficiency (GHD), which is of two types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD may result from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1 and HESX1. The present study reports on the molecular screening of GHRHR and GH1 in IGHD patients. METHODS A total of 116 clinically diagnosed IGHD patients and 100 controls were enrolled for the study after taking informed consent. Family history was noted and 5ml blood sample was drawn. Anatomical and/or morphological pituitary gland alterations were studied using magnetic resonance imaging (MRI). DNA from blood samples was processed for screening the GHRHR and GH1 by Sanger sequencing. RESULTS Mean age at presentation of the 116 patients (67 males and 49 females) was 11.71±3.5years. Mean height standard deviation score (SDS) and weight SDS were -4.5 and -3.5 respectively. Nine (7.8%) were familial and parental consanguinity was present in 21 (19.8%) families. Eighty-three patients underwent MRI and morphological alterations of the pituitary were observed in 39 (46.9%). GH1 and GHRHR screening revealed eleven variations in 24 (21%) patients of which, four were novel deleterious, one novel non-pathogenic and six reported changes. CONCLUSIONS GHRHR contributed more to IGHD in our patients which confirmed that GHRHR should be screened first before GH1 in our population. Identification of GH1 and GHRHR variations helped in defining our mutational spectrum which will play a crucial role in providing predictive and prenatal genetic testing to the patients.