Dyslipidemia in diabetes.

Diabetes mellitus is a metabolic disorder that often predisposes to cardiovascular diseases (CVD). CVD is an important cause of morbidity and mortality in diabetes. The typical diabetic dyslipidaemia is characterized by low HDL cholesterol, high triglycerides with mildly increased or even normal LDL. This attenuated rise in LDL is due to the more atherogenic small dense LDL particles. Genetic factors, obesity, lack of physical activity, alcohol abuse, poorly controlled glucose levels are some of the common risk factors for dyslipidaemia. Non-pharmacological management of dyslipidaemia is important and includes modification in the diet, increase in physical activity and efforts to reduce weight. Statins remain the mainstay of pharmacotherapy for dyslipidaemia in diabetes. Due to the small dense LDL, even patients with diabetes who have normal LDL cholesterol, achieve reduction in cardiovascular risk with statin therapy. Those patients who do not achieve acceptable LDL reductions with statin alone can be treated with combination therapy of ezetimibe with statins. Many novel therapies have also emerged such as bempedoic acid and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors. The targets for LDL cholesterol depend upon the patients underlying cardiovascular risk category. The use of pharmacotherapy for lowering triglycerides in patients with mild to moderate hypertriglyceridemia and diabetes is still a matter of debate. Proper management of dyslipidaemia is critical component of treatment of diabetes mellitus.

Phenotypic clusters of type 2 diabetes mellitus among North Indians reveal higher levels of insulin deficiency along with insulin resistance.

BACKGROUND: Type 2 diabetes is now considered a heterogenous disease. Distinct clusters have been identified with patterns varying between Europeans and South Asians as well as between South Indians who have described a novel cluster; Combined Insulin-Resistant and Deficient Diabetes, and individuals from West and East India who have reported that insulin deficiency is the primary driver of heterogeneity. Therefore, North Indian patients may also have a distinct, novel clustering pattern due to unique genetic, epigenetic, and environmental factors. We aim to identify clusters of type 2 diabetes in North Indians and to describe the different characteristics of these clusters. METHODS: The K value for the optimal number of clusters was obtained from two-step clustering. K means clustering was done with this K value using SPSS 29.0 software. Variables used for clustering were age, BMI, HbA1c, HOMA-beta, HOMA-IR, and waist circumference. RESULTS: Four phenotypically different clusters were identified in 469 individuals with type 2 diabetes. Cluster 1 was severe insulin deficient diabetes (15%), Cluster 2 was severe insulin resistant diabetes (22%), Cluster 3 was moderate obesity-related diabetes (35%), and Cluster 4 was moderate age-related diabetes (27%). Clusters 1 and 2 were similar to earlier studies but in different proportions. Clusters 3 and 4 characteristics were different from earlier studies, with greater impairment in beta cell function and higher HbA1c levels. Significant insulin resistance was noted in all clusters. CONCLUSION: The phenotypic clusters of type 2 diabetes identified in the present study were characterized by high levels of insulin deficiency along with important contributions from insulin resistance.

Efficacy and Safety of Osilodrostat in Managing Cushing's Syndrome: A Systematic Review and Meta-Analysis.

No meta-analysis has holistically analysed and summarized the efficacy and safety of osilodrostat, a novel dual 11ß-hydroxylase (cytochrome P450 family 11 subfamily B member 1 [CYP11B1]) and 18-hydroxylase (aldosterone synthase, CYP11B2) inhibitor in managing Cushing's syndrome (CS). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for randomized controlled trials (RCTs) involving patients with CS receiving osilodrostat in the intervention arm. The primary outcome was to evaluate changes in urine free cortisol (UFC) levels. Secondary outcomes were to evaluate alterations in cortisol levels, androgen levels, mineralocorticoid levels, and adverse events. From initially screened 109 articles, data from 2 RCTs involving 144 patients was analysed. After 8-12 weeks of therapy, the odds of achieving a normal 24-hour UFC was higher in patients receiving oslidrostat as compared to placebo. [odds ratio (OR) 21.94 (95% CI: 8.53-56.43); P < 0.00001; I2 = 0%]. The occurrence of adverse events [OR 1.35 (95% CI: 0.52-3.53); P = 0.54; I2 = 0%; low heterogeneity (LH); High certainty of evidence (HCE)], serious adverse events (SAEs) [OR 1.32 (95% CI: 0.30-5.79); P = 0.72; I2 = 0%; LH; HCE], adrenal insufficiency [OR 5.38 (95% CI: 0.91-31.78); P = 0.06; I2 = 0%; LH; HCE], headache [OR 0.98 (95% CI: 0.35-2.76); P = 0.97; I2 = 0%; LH; HCE], hyperandrogenism [OR 3.68 (95% CI: 0.59-22.80); P = 0.16; I2 = 0%; LH; HCE] and deaths [OR 0.32 (95% CI: 0.01-8.00); P = 0.48; I2 = 0%; LH; HCE] was comparable among the groups. The occurrence of nausea [OR 4.25 (95% CI: 1.26-14.30); P = 0.02; I2 = 0%; LH] and arthralgia [OR 6.54 (95% CI: 1.64-26.13); P = 0.008; I2 = 0%; LH; HCE] was significantly higher in the osilodrostat group as compared to placebo. Osilodrostat has good efficacy and safety in CS and was well tolerated over 48 weeks of use.

Can Bone-Specific Alkaline Phosphatase be a Marker of Vascular Calcification in Type 2 Diabetes Mellitus?

Background and Aims: Alkaline phosphatase (ALP) enzyme has been linked to vascular calcification. Unexplained elevations in serum ALP levels have been reported in patients with type 2 diabetes mellitus (T2DM). We assessed bone-specific alkaline phosphatase (BAP) levels in patients with T2DM who had unexplained ALP elevations and studied the association between BAP and other markers of vascular calcification. Methods: Patients with T2DM who had high serum ALP in the absence of known causes of ALP elevation were studied. The control group was T2DM patients with normal ALP. We measured the serum levels of BAP along with the leptin, fetuin-A, and vitamin K2 levels. Ankle-brachial index (ABI) was also measured in both groups. Results: Serum BAP levels were significantly higher in the group with high ALP when compared with the normal ALP group. A significant positive correlation was present between BAP and serum fetuin-A as well as between BAP and Vit K2 levels. There was no correlation between BAP and serum leptin. ABI was comparable between the two groups. Conclusions: Patients with T2DM may have unexplained elevation in ALP due to an increase in BAP. Elevation in BAP may be associated with other markers of vascular calcification suggesting an increased risk of vascular calcification.

Verapamil improves One-Year C-Peptide Levels in Recent Onset Type-1 Diabetes: A Meta-Analysis.

Meta-analysis studying the role of verapamil in improving C-peptide in people with recent-onset type-1 diabetes (T1DM) has not been conducted to date. We undertook this meta-analysis to address this knowledge gap. Electronic databases were systematically reviewed for RCTs having individuals with T1DM receiving verapamil in the treatment arm and placebo in the control arm over the standard of care. The primary outcome was to evaluate changes in the C-peptide area under the curve (AUC) at a one-year follow-up. Secondary outcomes were to assess alterations in C-peptide AUC, glycated hemoglobin (HbA1c), blood pressure, heart rate, and side effects at different time intervals over a one-year follow-up. From the initially screened 27 articles, data from two RCTs (112 patients) satisfied the inclusion criteria and were analyzed. Compared to placebo, C-peptide AUC in individuals receiving verapamil was not different at three months [MD 0.17 nmol/L (95%CI: -0.05-0.38); P = 0.13; I2 = 86%] but significantly higher at 1-year [MD 0.27 nmol/L (95%CI: 0.19-0.35); P < 0.01; I2 = 12%]. The verapamil arm showed similar changes in HbA1C at three months [MD 0.23% (95%CI: -0.43-0.90); P = 0.49; I2 = 88%] and 1-year [MD 0.18% (95% CI: -0.74 - 1.10); P = 0.70; I2 = 89%] compared to placebo. Occurrence of treatment-emergent adverse events [Risk ratio (RR) 1.90 (95%CI: 0.52-6.91); P = 0.33; I2 = 63%], serious adverse events [RR 1.40 (95%CI: 0.50-3.93); P = 0.53], constipation [RR4.11 (95%CI: 0.93-18.13); P = 0.06; I2 = 0%], headache [RR0.48 (95%CI: 0.16-1.43); P = 0.19; I2 = 0%], severe hypoglycemia [RR 0.87 (95%CI: 0.06 - 13.51); P = 0.92] were comparable across groups. Verapamil was well tolerated, and its use over one year was associated with significant improvements in C-peptide AUC though the HbA1c remained unchanged.

High level of psychological stress in COVID-19 recovered individuals: role of copeptin as a potential biomarker.

Background: Study aimed to assess stress in COVID-19 recovered individuals using a validated questionnaire PSS-10 score and stress biomarkers - salivary cortisol and serum copeptin. Methods: A total of 83 subjects of which 54 subjects (66.3%) who were hospitalized were recruited 8-20 weeks following recovery from COVID-19. Stress was assessed by PSS-10 stress-scale after a mean duration of 14.5 weeks after recovery. Sixty-eight subjects (81.9%) had new or persistent symptoms after recovery. Subjects were divided into two groups on the basis of PSS score; mild stress (PSS:0-13) and moderate to severe stress (PSS:>14) and levels of biomarkers (serum copeptin, DHEAS and salivary cortisol) were compared in the two groups. Results: Forty-four subjects (53%) had moderate to severe stress and 39 subjects (47%) had mild stress. Subjects with post COVID symptoms had significantly higher stress levels as compared to subjects who were asymptomatic [15 vs. 9; p = 0.003]. Serum copeptin levels were significantly higher among subjects with moderate to severe stress as compared to those with mild stress [0.41 vs. 0.67 ng/mL; p = 0.031]. Subjects with moderate to severe stress had higher median salivary cortisol compared to subjects with mild stress [1.03 vs. 1.44 nmol/L; p = 0.448]. Conclusion: Our study demonstrated moderate to severe stress in over half and some level of stress in nearly all COVID recovered individuals even after 3 months. Serum copeptin was found to be a useful biomarker to objectively measure stress in these subjects.

Diabetes reversal: Update on current knowledge and proposal of prediction score parameters for diabetes remission.

BACKGROUND AND AIM: The field of diabetes reversal is continuously evolving. Strategies for implementing diabetes care towards diabetes reversal are still being worked out. We aim to analyse data from available literature to ascertain factors allowing patient centric dietary approach to achieve diabetes reversal in clinical practice. METHODS: In this exploratory review, an update on current knowledge is presented to delineate factors driving diabetes remission in an individual based on major studies in the field. This knowledge is then applied to subtypes of type 2 diabetes to optimise dietary approach for reversal of diabetes. RESULTS AND CONCLUSION: Shorter duration of diabetes, lesser number of medicines needed to achieve euglycemia and 15 kg weight loss are common factors favouring diabetes remission in all major studies. A patient centric approach to diabetes reversal taking into account the recently described diabetes subtypes is being proposed to improve the proportion of patients achieving remission. We also propose the parameters of a novel diabetes remission prediction score, based on patient motivation, interaction with the care-team, level of diabetes self-care and the intent of the care-team.

Prevalence of diabetes related vascular complications in subjects with normal glucose tolerance, prediabetes, newly detected diabetes and known diabetes.

AIMS: Varying prevalence of individual diabetes related vascular complications in prediabetes has been reported. However, very few studies have looked at both macrovascular and microvascular complications in prediabetes. METHODS: Study subjects without any history of diabetes underwent oral glucose tolerance test (OGTT) and were classified as either normal glucose tolerance (NGT), prediabetes (PD), newly detected diabetes mellitus (NDDM) on the basis of American Diabetes Association (ADA) criteria. Age and sex matched known diabetes mellitus (KDM) patients were also recruited. All the participants were subsequently screened for both macrovascular (CAD, CVA,PVD) and microvascular (retinopathy, nephropathy and neuropathy)complications of diabetes. RESULTS: Prevalence of vascular complications among prediabetes subjects was 11.1% as compared to 1.4% among NGT subjects, 13.9% among NDDM subjects and 23.8% among KDM subjects. There was no significant between complication rates in prediabetes and NDDM group (p = 0.060). The prevalence of macrovascular and microvascular complications among prediabetes subjects was 4.2% and 6.9% while the same in NDDM was 4.2% and 9.7%. CONCLUSIONS: The proportion of subjects with prediabetes and vascular complications was about half of those with known diabetes and almost similar to those with newly detected diabetes mellitus.

Changing Trend in Vitamin D Status from 2008 to 2016: An Experience from a Tertiary Care Institute in North India.

BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) assays have become readily available in India over the past decade. A large number of cross-sectional studies have been performed on the vitamin D status and the prevalence of vitamin D deficiency (VDD) in India. However, seasonal and long-term trends in serum 25(OH)D levels have been reported less frequently. AIM: To determine the seasonal and year-wise variation in vitamin D status at a tertiary care hospital in north India. MATERIALS AND METHODS: Using hospital records, the data on serum 25(OH) D assays performed in its endocrinology laboratory between 2008 and 2016 were obtained. For analysis of seasonal trends, the months of a year were divided into following seasons: March to June (summer season), July to October (rainy season), and November to February (winter season). VDD was defined as serum 25(OH)D concentration <20 ng/mL. RESULTS: A total of 26,339 assays of serum 25(OH)D were analyzed in the study. The year-wise assay numbers increased steadily from 2008 to peak in the year 2012, followed by a decline and a second smaller peak in the year 2016. The mean serum 25(OH)D concentration increased from 19.1 ± 16.4 ng/mL in 2008 to 21.7 ± 17.1 ng/mL in 2016 (P = 0.02). Between 2008 and 2016, the prevalence of VDD decreased from 71.9% to 54.3% in females, and from 56.7% to 52.1% in males. The levels in rainy season were significantly higher as compared to winters and summers (P < 0.05 for both). Hypervitaminosis D (serum 25(OH)D >100 ng/mL) and vitamin D toxicity (serum 25(OH)D >150 ng/mL) were seen in 319 (1.2%) and 27 (0.1%) assays, respectively. CONCLUSIONS: This study provides data on seasonal and year-wise trends in vitamin D status over a long period of time at a tertiary care hospital in north India. A long-term trend toward improving vitamin D status, especially in females, was noted in the study. The prevalence of VDD was found to decrease in the analyzed samples during the study period.

Goiter Prevalence and Thyroid Autoimmunity in School Children of Delhi.

INTRODUCTION: Several studies from India, performed prior to 2010, have reported a goiter prevalence of greater than five per cent in school going children. There has been considerable success in universal salt iodization efforts in the past decade. We studied the prevalence of goiter and thyroid autoimmunity in school going children in Delhi between 2010 and 2014 to assess the impact of salt iodization. MATERIALS AND METHODS: The study employed the population proportionate to size (PPS) cluster sampling methodology to select subjects between the age of six and 14 years, from all 34 wards of 9 districts of Delhi. Cluster randomization sampling design was followed and in this way we identified 30 wards, from each of which 90 children were recruited for the study. The total sample size was 2700 children. Estimation of fT3, fT4, TSH, anti-TPO antibodies and urine iodine concentration (UIC) was done for 10% of the study population. RESULTS: The prevalence of goiter in this study in the 6-14 years age group was 6.4%. The prevalence of goiter was higher in females (7.7% compared to 5.3% in males, P = 0.01). In the 270 subjects who were selected for biochemical evaluation, subclinical hypothyroidism was seen in 18.4% and positive anti-TPO antibodies were seen in 14.8%. The median UIC was 150 µg/L. CONCLUSIONS: There is improvement in goiter prevalence in the post-iodization period in Delhi. But still, residual goiter rates are above five per cent suggesting presence of other causes of goiter in this area. There is a high prevalence of thyroid autoimmunity in this population.

Prediction of Gestational Diabetes from First Trimester Serum Adiponectin Levels in Indian Women.

INTRODUCTION: The prediction of gestational diabetes mellitus (GDM) by serum adiponectin levels has shown promise in Western literature. This study looks at the first trimester serum adiponectin levels as a predictor of gestational diabetes in Indian women. MATERIAL AND METHODS: A total of 450 pregnant women were screened at 11-- 13 weeks of gestation and serum samples were stored. All the women underwent an oral glucose tolerance test to diagnose GDM by International Association of Diabetes and Pregnancy study Group criteria at 24-- 28 weeks of gestation. Amongst these, 45 women who had developed GDM were compared with 45 controls. The first trimester serum adiponectin levels were compared between the two groups. RESULTS: Mean first trimester adiponectin in GDM and non-GDM group was 7.21 ± 2.49 µg/ml and 12.20 ± 2.91 µg/ml, respectively (P < 0.001). Logistic regression revealed that low adiponectin was the strongest independent risk factor followed by body mass index and HbA1c. Receiver operating characteristic curve revealed that a cut-off value of adiponectin of 9.10 µg/ml in the first trimester was associated with a sensitivity of 100% and specificity of 95.6% in predicting GDM. CONCLUSIONS: This is the first study from India which has studied the prediction of GDM by first trimester adiponectin levels. First trimester serum adiponectin may be a strong predictor of GDM in Asian Indian women.

Slipped Capital Femoral Epiphysis in Primary Hyperparathyroidism - Case Report with Literature Review.

Primary hyperparathyroidism is not common in children and adolescents. Association of slipped capital femoral epiphysis and hyperparathyroidism is rare. We report the case of a 15-year-old boy who presented with pain in both hips and limping. He was diagnosed to have bilateral slipped capital femoral epiphysis (SCFE) and underwent cancellous screw fixation of both hips. He had proximal myopathy and pain at multiple points over the chest. Examination revealed an emaciated patient with genu valgum, rachitic rosary, Harrison's sulcus, and bony tenderness over the ribs. Investigations showed PTH-dependent hypercalcemia with serum calcium levels reaching >17 mg/dL and electrocardiography showing QTc shortening. Imaging revealed parathyroid adenoma. The work up for multiple endocrine neoplasia syndromes (MEN) was negative. Serum calcium was controlled by medical management and patient underwent expedited surgery. Postoperatively serum calcium levels normalized and patient became better biochemically and clinically including resolution of skeletal changes on follow-up. Only 12 cases of SCFE associated with primary hyperparathyroidism have been reported worldwide till date including the current case. The literature has been reviewed and it indicates that SCFE is associated with late adolescent age and severe hyperparathyroidism (severe bone disease, higher parathormone, serum calcium, and alkaline phosphatase levels).

Invasive fungal rhinosinusitis in patients with diabetes.

INTRODUCTION: We report the clinical and radiological features as well as outcomes of invasive fungal rhinosinusitis in patients with diabetes from a tertiary care center in North India. METHODOLOGY: All patients admitted with a diagnosis of invasive fungal rhinosinusitis with pre-existing or newly diagnosed diabetes from 1st January 2008 to 31st December 2015 were included. Hospital records were used to identify clinical features, biochemical investigations and treatment modalities used. The imaging findings were reported at baseline, 30, 60,90 and 120 days of admission and progression of disease was reported as static, worse or improved. The outcomes were sight loss and survival at end of hospital stay. RESULTS: 22 patients of invasive fungal sinusitis and diabetes were identified. At presentation, 5 had ketoacidosis, all of whom died at the end of hospital stay. Loss of vision in one eye was seen in 70% cases. The survival at end of hospital stay was 72.7% and at six months after end of study period was 57.8%. No patients had radiological improvement at day 30 imaging (including those who subsequently improved). CONCLUSION: Radiological improvement is not apparent before two months of therapy. Ketoacidosis is a predictor of mortality in invasive fungal sinusitis with diabetes.

Prevalence and Associations of Hypothyroidism in Indian Patients with Type 2 Diabetes Mellitus.

Both type 2 diabetes and hypothyroidism are highly prevalent disorders in the community. The existing data regarding prevalence of hypothyroidism in patients with diabetes comes mostly from small studies. There are only two studies with a sample size of more than 1000 diabetic patients, none of which have been done in South Asians. The present study evaluated patients with type 2 diabetes for presence of hypothyroidism and the clinical factors associated with it. The demographic, anthropometric, clinical, and biochemical parameters of consecutively enrolled patients with diabetes were systematically collected and analyzed. A total of 1152 middle aged patients with type 2 diabetes with a mean duration of diabetes of around 10 years were enrolled. Nearly 40 percent of the patients were obese and overweight, respectively, for South Asian standards and abdominal obesity was seen in around 90% patients. Clinical hypothyroidism (TSH>10 mIU/ml) was present in 113 of patients (9.83%) and another 68 patients (5.9%) had subclinical hypothyroidism (TSH 5-10 mIU/ml). Anemia (odds ratio : 2.19), overweight/obese status (odds ratio 2.07), and known dyslipidemia (odds ratio : 1.99) were found to have independent association with clinical hypothyroidism. HbA1c, abdominal obesity, poor control of hypertension, lipid parameters, microalbuminuria, and renal dysfunction showed no difference among patients with hypothyroidism when compared with euthyroid patients. Subclinical hypothyroid patients had no difference in any of the above analyzed parameters when compared to the euthyroid patients. This study shows that a significant proportion of type 2 diabetes patients suffer from clinical or subclinical hypothyroidism and screening for the same may be appropriate.